TY  - JOUR
AB  - Getting mature and functional stem cell-derived, insulin-producing β cells is an important step for disease modeling, drug screening, and cell replacement therapy. In this issue, Hua et al.1 used single-cell multiomics analysis coupled with chemical screening to identify a crucial role for ceramides in generating mature stem cell-derived β cells.
AU  - Karampelias, C.
AU  - Lickert, H.
C1  - 70799
C2  - 55659
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 793-794
TI  - Greasing the machinery toward maturation of stem cell-derived β cells.
JO  - Cell Stem Cell
VL  - 31
IS  - 6
PB  - Cell Press
PY  - 2024
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient-specific HNF1A+/R272C β cells hypersecrete insulin both in vitro and in vivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 β cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 β cells. Our findings identify a pathogenic mechanism leading to β cell failure in MODY3.
AU  - Hermann, F.M.*
AU  - Kjærgaard, M.F.*
AU  - Tian, C.
AU  - Tiemann, U.*
AU  - Jackson, A.*
AU  - Olsen, L.R.*
AU  - Kraft, M.*
AU  - Carlsson, P.O.*
AU  - Elfving, I.M.*
AU  - Kettunen, J.L.T.*
AU  - Tuomi, T.*
AU  - Novak, I.*
AU  - Semb, H.
C1  - 67131
C2  - 53493
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 38-51.e8
TI  - An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells.
JO  - Cell Stem Cell
VL  - 30
IS  - 1
PB  - Cell Press
PY  - 2023
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Regenerating the lungs' architecture after injury requires rebuilding its fibroelastic extracellular matrix scaffold. Konkimalla et al. establish that regenerative cell states (RCSs) of both epithelial and mesenchymal origin are functionally linked and indispensable for this process. Experimental ablation of RCSs causes organ degeneration, whereas their induction causes organ fibrosis.
AU  - Schniering, J.
AU  - Schiller, H. B.
C1  - 68724
C2  - 54933
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1397-1399
TI  - Multilineage circuits of regenerative cell states.
JO  - Cell Stem Cell
VL  - 30
IS  - 11
PB  - Cell Press
PY  - 2023
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development and compare them with the in vivo embryo. We developed a high-throughput handling and imaging pipeline to spatially monitor symmetry breaking during gastruloid development and report an early spatial variability in pluripotency determining a binary response to Wnt activation. Although cells in the gastruloid-core revert to pluripotency, peripheral cells become primitive streak-like. These two populations subsequently break radial symmetry and initiate axial elongation. By performing a compound screen, perturbing thousands of gastruloids, we derive a phenotypic landscape and infer networks of genetic interactions. Finally, using a dual Wnt modulation, we improve the formation of anterior structures in the existing gastruloid model. This work provides a resource to understand how gastruloids develop and generate complex patterns in vitro.
AU  - Suppinger, S.*
AU  - Zinner, M.*
AU  - Aizarani, N.*
AU  - Lukonin, I.*
AU  - Ortiz, R.*
AU  - Azzi, C.*
AU  - Stadler, M.B.*
AU  - Vianello, S.*
AU  - Palla, G.
AU  - Kohler, H.*
AU  - Mayran, A.*
AU  - Lutolf, M.P.*
AU  - Liberali, P.*
C1  - 67824
C2  - 54302
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 867-884.e11
TI  - Multimodal characterization of murine gastruloid development.
JO  - Cell Stem Cell
VL  - 30
IS  - 6
PB  - Cell Press
PY  - 2023
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Du et al. transplanted β cells derived from pluripotent stem cells in diabetic monkeys for the first time, as an intermediate stage toward clinical translation. They observed benefits unfolding over months but also observed immune rejection of the grafts by 5–6 months.
AU  - Grapin-Botton, A.
AU  - Ludwig, B.
C1  - 64723
C2  - 51909
SP  - 500-502
TI  - Stem cell-derived β cells go in monkeys.
JO  - Cell Stem Cell
VL  - 29
IS  - 4
PY  - 2022
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Personalized in vitro models for dysplasia and carcinogenesis in the pancreas have been constrained by insufficient differentiation of human pluripotent stem cells (hPSCs) into the exocrine pancreatic lineage. Here, we differentiate hPSCs into pancreatic duct-like organoids (PDLOs) with morphological, transcriptional, proteomic, and functional characteristics of human pancreatic ducts, further maturing upon transplantation into mice. PDLOs are generated from hPSCs inducibly expressing oncogenic GNAS, KRAS, or KRAS with genetic covariance of lost CDKN2A and from induced hPSCs derived from a McCune-Albright patient. Each oncogene causes a specific growth, structural, and molecular phenotype in vitro. While transplanted PDLOs with oncogenic KRAS alone form heterogenous dysplastic lesions or cancer, KRAS with CDKN2A loss develop dedifferentiated pancreatic ductal adenocarcinomas. In contrast, transplanted PDLOs with mutant GNAS lead to intraductal papillary mucinous neoplasia-like structures. Conclusively, PDLOs enable in vitro and in vivo studies of pancreatic plasticity, dysplasia, and cancer formation from a genetically defined background.
AU  - Breunig, M.*
AU  - Merkle, J.*
AU  - Wagner, M.*
AU  - Melzer, M.K.*
AU  - Barth, T.F.E.*
AU  - Engleitner, T.*
AU  - Krumm, J.*
AU  - Wiedenmann, S.
AU  - Cohrs, C.M.
AU  - Perkhofer, L.*
AU  - Jain, G.*
AU  - Krüger, J.*
AU  - Hermann, P.C.*
AU  - Schmid, M.*
AU  - Madácsy, T.*
AU  - Varga, A.*
AU  - Griger, J.*
AU  - Azoitei, N.*
AU  - Müller, M.*
AU  - Wessely, O.*
AU  - Robey, P.G.*
AU  - Heller, S.*
AU  - Dantes, Z.*
AU  - Reichert, M.*
AU  - Günes, C.*
AU  - Bolenz, C.*
AU  - Kuhn, F.*
AU  - Maléth, J.*
AU  - Speier, S.
AU  - Liebau, S.*
AU  - Sipos, B.*
AU  - Kuster, B.*
AU  - Seufferlein, T.*
AU  - Rad, R.*
AU  - Meier, M.
AU  - Hohwieler, M.*
AU  - Kleger, A.*
C1  - 61968
C2  - 50585
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1105-1124.e19
TI  - Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells.
JO  - Cell Stem Cell
VL  - 28
IS  - 6
PB  - Cell Press
PY  - 2021
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - The biological function and disease association of human endogenous retroviruses (HERVs) are largely elusive. HERV-K(HML-2) has been associated with neurotoxicity, but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation using CRISPR engineering to activate or repress its expression levels in a human-pluripotent-stem-cell-based system. We found that elevated HERV-K(HML-2) transcription is detrimental for the development and function of cortical neurons. These effects are cell-type-specific, as dopaminergic neurons are unaffected. Moreover, high HERV-K(HML-2) transcription alters cortical layer formation in forebrain organoids. HERV-K(HML-2) transcriptional activation leads to hyperactivation of NTRK3 expression and other neurodegeneration-related genes. Direct activation of NTRK3 phenotypically resembles HERV-K(HML-2) induction, and reducing NTRK3 levels in context of HERV-K(HML-2) induction restores cortical neuron differentiation. Hence, these findings unravel a cell-type-specific role for HERV-K(HML-2) in cortical neuron development.
AU  - Padmanabhan Nair, V.
AU  - Liu, H.*
AU  - Ciceri, G.*
AU  - Jungverdorben, J.*
AU  - Frishman, G.
AU  - Tchieu, J.*
AU  - Cederquist, G.Y.*
AU  - Rothenaigner, I.
AU  - Schorpp, K.K.
AU  - Klepper, L.
AU  - Walsh, R.M.*
AU  - Kim, T.W.*
AU  - Cornacchia, D.*
AU  - Ruepp, A.
AU  - Mayer, J.*
AU  - Hadian, K.
AU  - Frishman, D.*
AU  - Studer, L.*
AU  - Vincendeau, M.
C1  - 61937
C2  - 50420
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1566-1581.e8
TI  - Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3.
JO  - Cell Stem Cell
VL  - 28
IS  - 9
PB  - Cell Press
PY  - 2021
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Astrocyte-to-neuron conversion is a promising avenue for neuronal 
      replacement therapy. Neurons are particularly dependent on mitochondrial
       function, but how well mitochondria adapt to the new fate is unknown. 
      Here, we determined the comprehensive mitochondrial proteome of cortical
       astrocytes and neurons, identifying about 150 significantly enriched 
      mitochondrial proteins for each cell type, including transporters, 
      metabolic enzymes, and cell-type-specific antioxidants. Monitoring their
       transition during reprogramming revealed late and only partial 
      adaptation to the neuronal identity. Early dCas9-mediated activation of 
      genes encoding mitochondrial proteins significantly improved conversion 
      efficiency, particularly for neuron-enriched but not astrocyte-enriched 
      antioxidant proteins. For example, Sod1 not only improves the survival 
      of the converted neurons but also elicits a faster conversion pace, 
      indicating that mitochondrial proteins act as enablers and drivers in 
      this process. Transcriptional engineering of mitochondrial proteins with
       other functions improved reprogramming as well, demonstrating a broader
       role of mitochondrial proteins during fate conversion.
AU  - Russo, G.L.
AU  - Sonsalla, G.
AU  - Natarajan, P.
AU  - Breunig, C.
AU  - Bulli, G.
AU  - Merl-Pham, J.
AU  - Schmitt, S.*
AU  - Giehrl-Schwab, J.
AU  - Giesert, F.
AU  - Jastroch, M.*
AU  - Zischka, H.
AU  - Wurst, W.
AU  - Stricker, S.H.
AU  - Hauck, S.M.
AU  - Masserdotti, G.
AU  - Götz, M.
C1  - 60719
C2  - 49485
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 524-534.e7
TI  - CRISPR-mediated induction of neuron-enriched mitochondrial proteins boosts direct glia-to-neuron conversion.
JO  - Cell Stem Cell
VL  - 28
IS  - 3
PB  - Cell Press
PY  - 2021
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - The mammalian brain contains few niches for neural stem cells (NSCs) capable of generating new neurons, whereas other regions are primarily gliogenic. Here we leverage the spatial separation of the sub-ependymal zone NSC niche and the olfactory bulb, the region to which newly generated neurons from the sub-ependymal zone migrate and integrate, and present a comprehensive proteomic characterization of these regions in comparison to the cerebral cortex, which is not conducive to neurogenesis and integration of new neurons. We find differing compositions of regulatory extracellular matrix (ECM) components in the neurogenic niche. We further show that quiescent NSCs are the main source of their local ECM, including the multi-functional enzyme transglutaminase 2, which we show is crucial for neurogenesis. Atomic force microscopy corroborated indications from the proteomic analyses that neurogenic niches are significantly stiffer than non-neurogenic parenchyma. Together these findings provide a powerful resource for unraveling unique compositions of neurogenic niches.
AU  - Kjell, J.
AU  - Fischer-Sternjak, J.
AU  - Thompson, A.J.*
AU  - Friess, C.*
AU  - Sticco, M.J.*
AU  - Salinas, F.*
AU  - Cox, J.*
AU  - Martinelli, D.C.*
AU  - Ninkovic, J.
AU  - Franze, K.*
AU  - Schiller, H. B.
AU  - Götz, M.
C1  - 58097
C2  - 48074
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 277-293.e8
TI  - Defining the adult neural stem cell niche proteome identifies key regulators of adult neurogenesis.
JO  - Cell Stem Cell
VL  - 26
IS  - 2
PB  - Cell Press
PY  - 2020
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety of contexts. Hyposumoylation enhances pluripotency reprogramming in vitro and in vivo, increases lineage transdifferentiation, and facilitates leukemic cell differentiation. Suppressing sumoylation in embryonic stem cells (ESCs) promotes their conversion into 2-cell-embryo-like (2C-like) cells. During reprogramming to pluripotency, SUMO functions on fibroblastic enhancers to retain somatic transcription factors together with Oct4, Sox2, and Klf4, thus impeding somatic enhancer inactivation. In contrast, in ESCs, SUMO functions on heterochromatin to silence the 2C program, maintaining both proper H3K9me3 levels genome-wide and repression of the Dux locus by triggering recruitment of the sumoylated PRC1.6 and Kap/Setdb1 repressive complexes. Together, these studies show that SUMO acts on chromatin as a glue to stabilize key determinants of somatic and pluripotent states.
AU  - Cossec, J.C.*
AU  - Theurillat, I.*
AU  - Chica, C.*
AU  - Búa Aguín, S.*
AU  - Gaume, X.
AU  - Andrieux, A.*
AU  - Iturbide Martinez De Albeniz, A.
AU  - Jouvion, G.*
AU  - Li, H.*
AU  - Bossis, G.*
AU  - Seeler, J.S.*
AU  - Torres-Padilla, M.E.
AU  - Dejean, A.*
C1  - 54685
C2  - 45765
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 742-757.e8
TI  - SUMO safeguards somatic and pluripotent cell identities by enforcing distinct chromatin states.
JO  - Cell Stem Cell
VL  - 23
IS  - 5
PB  - Cell Press
PY  - 2018
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Skin affections after sulfur mustard (SM) exposure include erythema, blister formation and severe inflammation. An antidote or specific therapy does not exist. Anti-inflammatory compounds as well as substances counteracting SM-induced cell death are under investigation. In this study, we investigated the benzylisoquinoline alkaloide berberine (BER), a metabolite in plants like berberis vulgaris, which is used as herbal pharmaceutical in Asian countries, against SM toxicity using a well-established in vitro approach. Keratinocyte (HaCaT) mono-cultures (MoC) or HaCaT/THP-1 co-cultures (CoC) were challenged with 100, 200 or 300 mM SM for 1 h. Post-exposure, both MoC and CoC were treated with 10, 30 or 50 mu M BER for 24 h. At that time, supernatants were collected and analyzed both for interleukine (IL) 6 and 8 levels and for content of adenylate-kinase (AK) as surrogate marker for cell necrosis. Cells were lysed and nucleosome formation as marker for late apoptosis was assessed. In parallel, AK in cells was determined for normalization purposes. BER treatment did not influence necrosis, but significantly decreased apoptosis. Anti-inflammatory effects were moderate, but also significant, primarily in CoC. Overall, BER has protective effects against SM toxicity in vitro. Whether this holds true should be evaluated in future in vivo studies.
AU  - Petrik, D.
AU  - Myoga, M.H.*
AU  - Grade, S.
AU  - Gerkau, N.J.*
AU  - Pusch, M.
AU  - Rose, C.R.*
AU  - Grothe, B.*
AU  - Götz, M.
C1  - 53559
C2  - 44678
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
SP  - 865-878.e8
TI  - Epithelial sodium channel regulates adult neural stem cell proliferation in a flow-dependent manner.
JO  - Cell Stem Cell
VL  - 22
IS  - 6
PB  - Elsevier Ireland Ltd
PY  - 2018
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - The increasing prevalence of obesity and diabetes is an urgent worldwide health challenge. Now in Cell Stem Cell, Yue et al. (2017) report a proof-of-concept study using genetically engineered skin transplants that produce the incretin GLP-1 to prevent diet-induced obesity, suggesting a powerful approach for treating metabolic disorders.
AU  - Böttcher, A.
AU  - Lickert, H.
AU  - Tschöp, M.H.
C1  - 51674
C2  - 43482
SP  - 153-155
TI  - Engineering skin with skinny genes.
JO  - Cell Stem Cell
VL  - 21
IS  - 2
PY  - 2017
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - The ability to directly reprogram mature cells to alternative fates challenges concepts of how cell identities are maintained, erased, and acquired. Recent advances in understanding and overcoming hurdles to direct neuronal conversion have provided new insights into mechanisms that maintain cell identity programs and have enabled high efficiency reprogramming in vivo. We discuss key cell-intrinsic molecular and metabolic constraints that influence the establishment of a new identity as well as environmental inputs from injured brains that favor or harm the conversion process. Finally, we outline the challenges ahead with a particular focus on direct neuronal reprogramming in vivo.
AU  - Gascón, S.
AU  - Masserdotti, G.
AU  - Russo, G.L.
AU  - Götz, M.
C1  - 51488
C2  - 43257
CY  - Cambridge
SP  - 18-34
TI  - Direct neuronal reprogramming: Achievements, hurdles, and new roads to success.
JO  - Cell Stem Cell
VL  - 21
IS  - 1
PB  - Cell Press
PY  - 2017
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxidative stress response. Importantly, co-expression of Bcl-2 and anti-oxidative treatments leads to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type in vitro and in vivo.
AU  - Gascón, S.
AU  - Murenu, E.
AU  - Masserdotti, G.
AU  - Ortega, F.*
AU  - Russo, G.L.
AU  - Petrik, D.
AU  - Deshpande, A.*
AU  - Heinrich, C.*
AU  - Karow, M.*
AU  - Robertson, S.P.*
AU  - Schroeder, T.
AU  - Beckers, J.
AU  - Irmler, M.
AU  - Berndt, C.*
AU  - Friedmann Angeli, J.P.F.
AU  - Conrad, M.
AU  - Berninger, B.*
AU  - Götz, M.
C1  - 47665
C2  - 39416
CY  - Cambridge
SP  - 396-409
TI  - Identification and successful negotiation of a metabolic checkpoint in direct neuronal repogramming.
JO  - Cell Stem Cell
VL  - 18
IS  - 3
PB  - Cell Press
PY  - 2016
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - We asked six leaders in the reprogramming field to share their views on remaining gaps in our scientific understanding of iPSCs that will need to be addressed to achieve their clinical promise. Their insights echo many issues raised in the Review by Tapia and Scholer in this issue.
AU  - Wernig, M.*
AU  - Götz, M.
AU  - Eto, K.*
C1  - 50181
C2  - 42234
CY  - Cambridge
SP  - 291-292
TI  - Overcoming iPSC Obstacles.
JO  - Cell Stem Cell
VL  - 19
IS  - 3
PB  - Cell Press
PY  - 2016
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Reactive astrocytes (RAs) have been reported to convert to multipotent neural stem cells (NSCs) capable of neurosphere (NS) formation and multilineage differentiation in vitro. Using genetic tagging, we determined that subventricular zone (SVZ) NSCs give rise to NSs derived from the stroke-injured cortex. We demonstrate that these cells can be isolated from the cortex in two different models of stroke and from different stroke-lesioned cortical regions. Interestingly, SVZ NSCs give rise to a subpopulation of RAs in the cortex that contribute to astrogliosis and scar formation. Last, we show that these SVZ derived RAs can be converted to neurons in vivo by forced expression of Ascl1. Identifying the contribution of cells originating from the SVZ to injury repair has implications for neural regeneration strategies.
AU  - Faiz, M.*
AU  - Sachewsky, N.*
AU  - Gascón, S.
AU  - Bang, K.W.*
AU  - Morshead, C.M.*
AU  - Nagy, A.*
C1  - 47250
C2  - 40615
SP  - 624-634
TI  - Adult neural stem cells from the subventricular zone give rise to reactive astrocytes in the cortex after stroke.
JO  - Cell Stem Cell
VL  - 17
IS  - 5
PY  - 2015
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Direct lineage reprogramming induces dramatic shifts in cellular identity, employing poorly understood mechanisms. Recently, we demonstrated that expression of Neurog2 or Ascl1 in postnatal mouse astrocytes generates glutamatergic or GABAergic neurons. Here, we take advantage of this model to study dynamics of neuronal cell fate acquisition at the transcriptional level. We found that Neurog2 and Ascl1 rapidly elicited distinct neurogenic programs with only a small subset of shared target genes. Within this subset, only NeuroD4 could by itself induce neuronal reprogramming in both mouse and human astrocytes, while co-expression with Insm1 was required for glutamatergic maturation. Cultured astrocytes gradually became refractory to reprogramming, in part by the repressor REST preventing Neurog2 from binding to the NeuroD4 promoter. Notably, in astrocytes refractory to Neurog2 activation, the underlying neurogenic program remained amenable to reprogramming by exogenous NeuroD4. Our findings support a model of temporal hierarchy for cell fate change during neuronal reprogramming.
AU  - Masserdotti, G.
AU  - Gillotin, S.*
AU  - Sutor, B.*
AU  - Drechsel, D.*
AU  - Irmler, M.
AU  - Jørgensen, H.F.*
AU  - Sass, S.
AU  - Theis, F.J.
AU  - Beckers, J.
AU  - Berninger, B.*
AU  - Guillemot, F.*
AU  - Götz, M.
C1  - 45577
C2  - 37375
SP  - 74-88
TI  - Transcriptional mechanisms of proneural factors and REST in regulating neuronal reprogramming of astrocytes.
JO  - Cell Stem Cell
VL  - 17
IS  - 1
PY  - 2015
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Heterogeneity within the self-renewal durability of adult hematopoietic stem cells (HSCs) challenges our understanding of the molecular framework underlying HSC function. Gene expression studies have been hampered by the presence of multiple HSC subtypes and contaminating non-HSCs in bulk HSC populations. To gain deeper insight into the gene expression program of murine HSCs, we combined single-cell functional assays with flow cytometric index sorting and single-cell gene expression assays. Through bioinformatic integration of these datasets, we designed an unbiased sorting strategy that separates non-HSCs away from HSCs, and single-cell transplantation experiments using the enriched population were combined with RNA-seq data to identify key molecules that associate with long-term durable self-renewal, producing a single-cell molecular dataset that is linked to functional stem cell activity. Finally, we demonstrated the broader applicability of this approach for linking key molecules with defined cellular functions in another stem cell system.
AU  - Wilson, N.K.*
AU  - Kent, D.G.*
AU  - Buettner, F.
AU  - Shehata, M.*
AU  - Macaulay, I.C.*
AU  - Calero-Nieto, F.J.*
AU  - Sánchez Castillo, M.*
AU  - Oedekoven, C.A.*
AU  - Diamanti, E.*
AU  - Schulte, R.*
AU  - Ponting, C.P.*
AU  - Voet, T.*
AU  - Caldas, C.*
AU  - Stingl, J.*
AU  - Green, A.R.*
AU  - Theis, F.J.
AU  - Göttgens, B.*
C1  - 44969
C2  - 37110
CY  - Cambridge
SP  - 712-724
TI  - Combined single-cell functional and gene expression analysis resolves heterogeneity within stem cell populations.
JO  - Cell Stem Cell
VL  - 16
IS  - 6
PB  - Cell Press
PY  - 2015
SN  - 1934-5909
ER  - 

TY  - JOUR
AU  - Filipczyk, A.
AU  - Gkatzis, K.*
AU  - Fu, J.*
AU  - Hoppe, P.S.
AU  - Lickert, H.
AU  - Anastassiadis, K.*
AU  - Schroeder, T.
C1  - 27765
C2  - 32803
CY  - Cambridge
SP  - 12-13
TI  - Biallelic expression of nanog protein in mouse embryonic stem cells.
JO  - Cell Stem Cell
VL  - 13
IS  - 1
PB  - Cell Press
PY  - 2013
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.
AU  - Ninkovic, J.
AU  - Steiner-Mezzadri, A.
AU  - Jawerka, M.*
AU  - Akinci, U.*
AU  - Masserdotti, G.
AU  - Petricca, S.
AU  - Fischer, J.
AU  - von Holst, A.*
AU  - Beckers, J.
AU  - Lie, D.C.
AU  - Petrik, D.*
AU  - Miller, E.*
AU  - Tang, J.*
AU  - Wu, J.*
AU  - Lefebvre, V.*
AU  - Demmers, J.*
AU  - Eisch, A.*
AU  - Metzger, D.*
AU  - Crabtree, G.*
AU  - Irmler, M.
AU  - Poot, R.*
AU  - Götz, M.
C1  - 26597
C2  - 32294
SP  - 403-418
TI  - The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.
JO  - Cell Stem Cell
VL  - 13
IS  - 4
PB  - Cell Press
PY  - 2013
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - As a result of brain injury, astrocytes become activated and start to proliferate in the vicinity of the injury site. Recently, we had demonstrated that these reactive astrocytes, or glia, can form self-renewing and multipotent neurospheres in vitro. In the present study, we demonstrate that it is only invasive injury, such as stab wounding or cerebral ischemia, and not noninvasive injury conditions, such as chronic amyloidosis or induced neuronal death, that can elicit this increase in plasticity. Furthermore, we find that Sonic hedgehog (SHH) is the signal that acts directly on the astrocytes and is necessary and sufficient to elicit the stem cell response both in vitro and in vivo. These findings provide a molecular basis for how cells with neural stem cell lineage emerge at sites of brain injury and imply that the high levels of SHH known to enter the brain from extraneural sources after invasive injury can trigger this response.
AU  - Sirko, S.
AU  - Behrendt, G.*
AU  - Johansson, P.A.
AU  - Tripathi, P.
AU  - Costa, M.R.
AU  - Bek, S.
AU  - Heinrich, C.*
AU  - Tiedt, S.*
AU  - Colak, D.
AU  - Dichgans, M.*
AU  - Fischer, I.R.*
AU  - Plesnila, N.*
AU  - Staufenbiel, M.*
AU  - Haass, C.*
AU  - Snapyan, M.*
AU  - Saghatelyan, A.*
AU  - Tsai, L.H.*
AU  - Fischer, A.*
AU  - Grobe, K.*
AU  - Dimou, L.
AU  - Götz, M.
C1  - 24523
C2  - 31567
SP  - 426-439
TI  - Reactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog.
JO  - Cell Stem Cell
VL  - 12
IS  - 4
PB  - Cell Press
PY  - 2013
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.
AU  - Brookes, E.*
AU  - de Santiago, I.*
AU  - Hebenstreit, D.*
AU  - Morris, K.J.*
AU  - Carroll, T.*
AU  - Xie, S.Q.*
AU  - Stock, J.K.*
AU  - Heidemann, M.
AU  - Eick, D.
AU  - Nozaki, N.*
AU  - Kimura, H.*
AU  - Ragoussis, J.*
AU  - Teichmann, S.A.*
AU  - Pombo, A.*
C1  - 7229
C2  - 29576
SP  - 157-170
TI  - Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.
JO  - Cell Stem Cell
VL  - 10
IS  - 2
PB  - Elsevier
PY  - 2012
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.
AU  - Karow, M.*
AU  - Sánchez, R.*
AU  - Schichor, C.*
AU  - Masserdotti, G.
AU  - Ortega, F.*
AU  - Heinrich, C.*
AU  - Gascón, S.
AU  - Khan, M.A.
AU  - Lie, D.C.
AU  - Dellavalle, A.*
AU  - Cossu, G.*
AU  - Goldbrunner, R.*
AU  - Götz, M.
AU  - Berninger, B.
C1  - 10477
C2  - 30221
SP  - 471-476
TI  - Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells.
JO  - Cell Stem Cell
VL  - 11
IS  - 4
PB  - Elsevier 
PY  - 2012
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - The molecular mechanisms specifying hematopoietic stem cells (HSCs) in the vertebrate embryo remain poorly understood. Recently in Nature, Traver and colleagues demonstrate that timed wnt to Notch relay signaling across multiple cell types serves as an early upstream mechanism of HSC induction in zebrafish (Clements et al., 2011).
AU  - Loeffler, D.
AU  - Kokkaliaris, K.D.
AU  - Schroeder, T.
C1  - 6649
C2  - 29039
CY  - Cambridge, MA, USA
SP  - 2-4
TI  - Wnt to notch relay signaling induces definitive hematopoiesis.
JO  - Cell Stem Cell
VL  - 9
IS  - 1
PB  - Cell Press
PY  - 2011
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Until now, limitations in the ability to enrich adult NSCs (aNSCs) have hampered meaningful analysis of these cells at the transcriptome level. Here we show via a split-Cre technology that coincident activity of the hGFAP and prominin1 promoters is a hallmark of aNSCs in vivo. Sorting of cells from the adult mouse subependymal zone (SEZ) based on their expression of GFAP and prominin1 isolates all self-renewing, multipotent stem cells at high purity. Comparison of the transcriptome of these purified aNSCs to parenchymal nonneurogenic astrocytes and other SEZ cells reveals aNSC hallmarks, including neuronal lineage priming and the importance of cilia- and Ca-dependent signaling pathways. Inducible deletion of the ciliary protein IFT88 in aNSCs validates the role of ciliary function in aNSCs. Our work reveals candidate molecular regulators for unique features of aNSCs and facilitates future selective analysis of aNSCs in other functional contexts, such as aging and injury.
AU  - Beckervordersandforth-Bonk, R.
AU  - Tripathi, P.
AU  - Ninkovic, J.
AU  - Bayam, E.
AU  - Lepier, A.*
AU  - Stempfhuber, B.
AU  - Kirchhoff, F.*
AU  - Hirrlinger, J.*
AU  - Haslinger, A.
AU  - Lie, D.C.
AU  - Beckers, J.
AU  - Yoder, B.*
AU  - Irmler, M.
AU  - Götz, M.
C1  - 5602
C2  - 27967
SP  - 744-758
TI  - In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells.
JO  - Cell Stem Cell
VL  - 7
IS  - 6
PB  - Elsevier
PY  - 2010
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Hematopoiesis requires the interaction of hematopoietic stem cells (HSCs) with various stromal microenvironments. Here, we examine the role of early B cell factor 2 (Ebf2), a transcription factor expressed in a subset of immature osteoblastic cells. Ebf2(-/-) mice show decreased frequencies of HSCs and lineage-committed progenitors. This defect is cell nonautonomous, as shown by the fact that transplantation of Ebf2-deficient bone marrow into wild-type hosts results in normal hematopoiesis. In coculture experiments, Ebf2(-/-) osteoblastic cells have reduced potential to support short-term proliferation of HSCs. Expression profiling of sorted Ebf2(-/-) osteoblastic cells indicated that several genes implicated in the maintenance of HSCs are downregulated relative to Ebf2(+/-) cells, whereas genes encoding secreted frizzled-related proteins are upregulated. Moreover, wild-type HSCs cocultured with Ebf2(-/-) osteoblastic cells show a reduced Wnt response relative to coculture with Ebf2(+/-) cells. Thus, Ebf2 acts as a transcriptional determinant of an osteoblastic niche that regulates the maintenance of hematopoietic progenitors, in part by modulating Wnt signaling.
AU  - Kieslinger, M.
AU  - Hiechinger, S.
AU  - Dobreva, G.*
AU  - Consalez, G.G.*
AU  - Grosschedl, R.*
C1  - 4653
C2  - 27647
SP  - 496-507
TI  - Early B cell factor 2 regulates hematopoietic stem cell homeostasis in a cell-nonautonomous manner.
JO  - Cell Stem Cell
VL  - 7
IS  - 4
PB  - Elsevier
PY  - 2010
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - New neurons are generated in the adult hippocampus throughout life by neural stem/progenitor cells (NSCs), and neurogenesis is a plastic process responsive to external stimuli. We show that canonical Notch signaling through RBP-J is required for hippocampal neurogenesis. Notch signaling distinguishes morphologically distinct Sox2(+) NSCs, and within these pools subpopulations can shuttle between mitotically active or quiescent. Radial and horizontal NSCs respond selectively to neurogenic stimuli. Physical exercise activates the quiescent radial population whereas epileptic seizures induce expansion of the horizontal NSC pool. Surprisingly, reduced neurogenesis correlates with a loss of active horizontal NSCs in aged mice rather than a total loss of stem cells, and the transition to a quiescent state is reversible to rejuvenate neurogenesis in the brain. The discovery of multiple NSC populations with Notch dependence but selective responses to stimuli and reversible quiescence has important implications for the mechanisms of adaptive learning and also for regenerative therapy.
AU  - Lugert, S.*
AU  - Basak, O.*
AU  - Knuckles, P.*
AU  - Haussler, U.*
AU  - Fabel, K.*
AU  - Götz, M.
AU  - Haas, C.A.*
AU  - Kempermann, G.*
AU  - Taylor, V.*
AU  - Giachino, C.*
C1  - 1304
C2  - 27362
SP  - 445-456
TI  - Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging.
JO  - Cell Stem Cell
VL  - 6
IS  - 5
PB  - Elsevier
PY  - 2010
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Neural stem cells (NSCs) in the adult hippocampus divide infrequently, and the molecules that modulate their quiescence are largely unknown. Here, we show that bone morphogenetic protein (BMP) signaling is active in hippocampal NSCs, downstream of BMPR-IA. BMPs reversibly diminish proliferation of cultured NSCs while maintaining their undifferentiated state. In vivo, acute blockade of BMP signaling in the hippocampus by intracerebral infusion of Noggin first recruits quiescent NSCs into the cycle and increases neurogenesis; subsequently, it leads to decreased stem cell division and depletion of precursors and newborn neurons. Consistently, selective ablation of Bmpr1a in hippocampal NSCs, or inactivation of BMP canonical signaling in conditional Smad4 knockout mice, transiently enhances proliferation but later leads to a reduced number of precursors, thereby limiting neuronal birth. BMPs are therefore required to balance NSC quiescence/proliferation and to prevent loss of the stem cell activity that supports continuous neurogenesis in the mature hippocampus.
AU  - Mira, H.*
AU  - Andreu, Z.*
AU  - Suh, H.*
AU  - Lie, D.C.
AU  - Jessberger, S.*
AU  - Consiglio, A.*
AU  - San Emeterio, J.*
AU  - Hortigüela, R.*
AU  - Marques-Torrejon, M.A.*
AU  - Nakashima, K.*
AU  - Colak, D.
AU  - Götz, M.
AU  - Farinas, I.*
AU  - Gage, F.H.*
C1  - 5408
C2  - 27556
SP  - 78-89
TI  - Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.
JO  - Cell Stem Cell
VL  - 7
IS  - 1
PB  - Cell Press
PY  - 2010
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Thanks to well-established quantitative functional assays and prospective isolation methods, hematopoietic stem cells (HSCs) are among the best understood stem cells. Nevertheless, recent studies have identified new HSC subtypes with distinct properties within previously characterized populations, leading us to question long-held views on the underlying basis of HSC heterogeneity.
AU  - Schroeder, T.
C1  - 4780
C2  - 27624
SP  - 203-207
TI  - Hematopoietic stem cell heterogeneity: Subtypes, not unpredictable behavior.
JO  - Cell Stem Cell
VL  - 6
IS  - 3
PB  - Elsevier
PY  - 2010
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Secreted frizzled-related protein 1 (Sfrp1) is highly expressed by stromal cells maintaining hematopoietic stem cells (HSCs). Sfrp1 loss in stromal cells increases production of hematopoietic progenitors, and in knockout mice, dysregulates hemostasis and increases Flk2- Cd34- Lin- Sca1+ Kit+ (LSK) cell numbers in bone marrow. Also, LSK and multipotent progenitors (MPPs) resided mainly in the G0/G1 phase of cell cycle, with an accompanying decrease in intracellular beta-catenin levels. Gene-expression studies showed a concomitant decrease Ccnd1 and Dkk1 in Cd34- LSK cells and increased expression of Pparg, Hes1, and Runx1 in MPP. Transplantation experiments showed no intrinsic effect of Sfrp1 loss on the number of HSCs or their ability to engraft irradiated recipients. In contrast, serial transplantations of wild-type HSCs into Sfrp1(-/-) mice show a progressive decrease of wild-type LSK and MPP numbers. Our results demonstrate that Sfrp1 is required to maintain HSC homeostasis through extrinsic regulation of beta-catenin.
AU  - Renström, J.*
AU  - Istvanffy, R.*
AU  - Gauthier, K.*
AU  - Shimono, A.*
AU  - Mages, J.*
AU  - Jardon-Alvarez, A.*
AU  - Kröger, M.*
AU  - Schiemann, M.
AU  - Busch, D.H.
AU  - Esposito, I.
AU  - Lang, R.*
AU  - Peschel, C.*
AU  - Oostendorp, R.A.*
C1  - 1663
C2  - 26640
CY  - Cambridge
SP  - 157-167
TI  - Secreted frizzled-related protein 1 extrinsically regulates cycling activity and maintenance of hematopoietic stem cells.
JO  - Cell Stem Cell
VL  - 5
IS  - 2
PB  - Cell Press
PY  - 2009
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Regulating the choice between neural stem cell maintenance versus differentiation determines growth and size of the developing brain. Here we identify TGF-beta signaling as a crucial factor controlling these processes. At early developmental stages, TGF-beta signal activity is localized close to the ventricular surface of the neuroepithelium. In the midbrain, but not in the forebrain, Tgfbr2 ablation results in ectopic expression of Wnt1/beta-catenin and FGF8, activation of Wnt target genes, and increased proliferation and horizontal expansion of neuroepithelial cells due to shortened cell-cycle length and decreased cell-cycle exit. Consistent with this phenotype, self-renewal of mutant neuroepithelial stem cells is enhanced in the presence of FGF and requires Wnt signaling. Moreover, TGF-beta signal activation counteracts Wnt-induced proliferation of midbrain neuroepithelial cells. Thus, TGF-beta signaling controls the size of a specific brain area, the dorsal midbrain, by antagonizing canonical Wnt signaling and negatively regulating self-renewal of neuroepithelial stem cells.
AU  - Falk, S.*
AU  - Wurdak, H.*
AU  - Ittner, L.M.*
AU  - Ille, F.*
AU  - Sumara, G.*
AU  - Schmid, M.-T.
AU  - Draganova, K.*
AU  - Lang, K.S.*
AU  - Paratore, C.*
AU  - Leveen, P.*
AU  - Suter, U.*
AU  - Karlsson, S.*
AU  - Born, W.*
AU  - Ricci, R.*
AU  - Götz, M.
AU  - Sommer, L.*
C1  - 780
C2  - 25402
SP  - 472-483
TI  - Brain area-specific effect of TGF-beta signaling on Wnt-dependent neural stem cell expansion.
JO  - Cell Stem Cell
VL  - 2
IS  - 5
PB  - Cell Press
PY  - 2008
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Pancreatic adenocarcinoma is currently the fourth leading cause for cancer-related mortality. Stem cells have been implicated in pancreatic tumor growth, but the specific role of these cancer stem cells in tumor biology, including metastasis, is still uncertain. We found that human pancreatic cancer tissue contains cancer stem cells defined by CD133 expression that are exclusively tumorigenic and highly resistant to standard chemotherapy. In the invasive front of pancreatic tumors, a distinct subpopulation of CD133+ CXCR4+ cancer stem cells was identified that determines the metastatic phenotype of the individual tumor. Depletion of the cancer stem cell pool for these migrating cancer stem cells virtually abrogated the metastatic phenotype of pancreatic tumors without affecting their tumorigenic potential. In conclusion, we demonstrate that a subpopulation of migrating CD133+ CXCR4+ cancer stem cells is essential for tumor metastasis. Strategies aimed at modulating the SDF-1/CXCR4 axis may have important clinical applications to inhibit metastasis of cancer stem cells.
AU  - Hermann, P.C.*
AU  - Huber, S.L.*
AU  - Herrler, T.*
AU  - Aicher, A.*
AU  - Ellwart, J.W.
AU  - Guba, M.*
AU  - Bruns, C.J.*
AU  - Heeschen, C.*
C1  - 1432
C2  - 24824
SP  - 313-323
TI  - Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.
JO  - Cell Stem Cell
VL  - 1
IS  - 3
PB  - Elsevier
PY  - 2007
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Pax6-positive radial glial (RG) cells are the progenitors of most glutamatergic neurons in the cortex, a lineage that can be recapitulated in vitro using embryonic stem (ES) cells. We show here that ES cells lacking Pax6, a transcription factor long known to be essential for cortical development, generate Mash1-positive RG cells that differentiate in GABAergic neurons. These neurons express high levels of the neurotrophin receptor p75NTR causing their rapid death. Pax6 function was also investigated following transplantation of ES cells in the developing chick telencephalon and in mice lacking both Pax6 and p75NTR. Taken together, our results indicate that reliable predictions can be made with cultured ES cells when used to explore the role of genes impacting early aspects of mammalian neurogenesis. They also provide a novel opportunity to compare the molecular constituents of glutamatergic with those of GABA-ergic neurons and to explore the mechanisms of their generation.
AU  - Nikoletopoulou, V.*
AU  - Plachta, N.*
AU  - Allen, N.D.*
AU  - Pinto, L.
AU  - Götz, M.
AU  - Barde, Y.A.*
C1  - 2557
C2  - 24970
SP  - 529-540
TI  - Neurotrophin receptor-mediated death of misspecified neurons generated from embryonic stem cells lacking Pax6.
JO  - Cell Stem Cell
VL  - 1
IS  - 5
PB  - Elsevier
PY  - 2007
SN  - 1934-5909
ER  - 

TY  - JOUR
AB  - Abstract
AU  - Schroeder, T.
C1  - 3809
C2  - 24812
SP  - 479-481
TI  - Asymmetric cell division in normal and malignant hematopoietic precursor cells.
JO  - Cell Stem Cell
VL  - 1
IS  - 5
PB  - Elsevier
PY  - 2007
SN  - 1934-5909
ER  -