TY - JOUR AB - Pancreatic islets consist of several different endocrine cell types that work in harmony. Aside from primary pancreatic islets, stem cell-derived pancreatic islets can be used as an alternative research and disease model. Here, we introduce a double reporter line of ARX-T2A-H2B-CFP x C-PEP-mCherry-hiPSC through CRISPR/Cas9-mediated insertion of mCherry in the C-terminus of C-Peptide in the previously published ARX-CFP hiPSC line. This reporter line allows live monitoring of stem cell-derived pancreatic alpha and beta cells throughout differentiation. AU - Setyono, E.S.A. AU - Rogers, N.K. AU - Hofmann, A. AU - Lickert, H. AU - Burtscher, I. C1 - 73581 C2 - 57125 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of ARX-T2A-H2B-CFP x C-PEP-mCherry-hiPSC double reporter line for monitoring of pancreatic differentiation. JO - Stem Cell Res. VL - 84 PB - Elsevier PY - 2025 SN - 1873-5061 ER - TY - JOUR AB - Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN) is a lethal neurodegenerative disorder caused by mutations in the human gene C19orf12. The molecular mechanisms underlying the disorder are still unclear, and no established therapy is available. Here, we describe the generation and characterization of two human induced pluripotent stem cell (iPSC) lines derived from skin fibroblasts of two MPAN patients carrying homozygous recessive mutations in C19orf12. These iPSC lines represent a useful resource for future investigations on the pathology of MPAN, as well as for the development of successful treatments. AU - Zanuttigh, E. AU - Rusha, E. AU - Peron, C.* AU - Brunetti, D.* AU - Zorzi, G.* AU - Pertek, A. AU - Nteli, P. AU - Winkelmann, J. AU - Tiranti, V.* AU - Iuso, A. C1 - 68251 C2 - 54715 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of two human iPSC lines, HMGUi004-A and FINCBi004-A, from fibroblasts of MPAN patients carrying pathogenic recessive mutations in the gene C19orf12. JO - Stem Cell Res. VL - 72 PB - Elsevier PY - 2023 SN - 1873-5061 ER - TY - JOUR AB - Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the de novo coenzyme A (CoA) synthesis starting from pantothenate. Mutations in PPCS cause autosomal-recessive dilated cardiomyopathy, often fatal, without apparent neurodegeneration, whereas pathogenic variants in PANK2 and COASY, two other genes involved in the CoA synthesis, cause Neurodegeneration with Brain Iron Accumulation (NBIA). PPCS-deficiency is a relatively new disease with unclear pathogenesis and no targeted therapy. Here, we report the generation of induced pluripotent stem cells from fibroblasts of two PPCS-deficient patients. These cellular models could represent a platform for pathophysiological studies and testing of therapeutic compounds for PPCS-deficiency. AU - Iuso, A. AU - Zhang, F.* AU - Rusha, E. AU - Campbell, B.* AU - Dorn, T.* AU - Zanuttigh, E. AU - Haas, D.* AU - Anikster, Y.* AU - Lederer, G.* AU - Pertek, A. AU - Nteli, P. AU - Laugwitz, K.L.* AU - Moretti, A.* C1 - 64753 C2 - 52437 TI - Generation of two human iPSC lines, HMGUi003-A and MRIi028-A, carrying pathogenic biallelic variants in the PPCS gene. JO - Stem Cell Res. VL - 61 PY - 2022 SN - 1873-5061 ER - TY - JOUR AB - The peptide hormone insulin produced by pancreatic β-cells undergoes post-transcriptional processing before secretion. In particular, C-peptide is cleaved from pro-insulin to generate mature insulin. Here, we introduce a C-peptide-mCherry human iPSC line (HMGUi001-A-8). The line was generated by CRISPR/Cas9 mediated heterozygous insertion of the mCherry sequence into exon 3 of the insulin locus. We demonstrate that the line is pluripotent and efficiently differentiates towards pancreatic β-like cells, which localize a red fluorescent C-peptide-mCherry fusion protein in insulin containing granules. Hence, the HMGUi001-A-8 line is a valuable resource to purify derived β-like cells and follow insulin-containing granules in real time. AU - Siehler, J. AU - Blöchinger, A. AU - Akgün, M. AU - Wang, X. AU - Shahryari, A. AU - Geerlof, A. AU - Lickert, H. AU - Burtscher, I. C1 - 60892 C2 - 49733 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of a heterozygous C-peptide-mCherry reporter human iPSC line (HMGUi001-A-8). JO - Stem Cell Res. VL - 50 PB - Elsevier PY - 2021 SN - 1873-5061 ER - TY - JOUR AB - Differentiating human induced pluripotent stem cells (hiPSCs) into insulin (INS)-producing beta-like cells has potential for diabetes research and therapy. Here, we generated a heterozygous fluorescent hiPSC reporter, labeling INS-producing beta-like cells. We used CRISPR/Cas9 technology to knock-in a T2A-H2B-Cherry cassette to replace the translational INS stop codon, enabling co-transcription and T2A-peptide mediated co-translational cleavage of INS-T2A and H2B-Cherry. The hiPSC-INS-T2A-H2B-Cherry reporter cells were pluripotent and showed multi-lineage differentiation potential. Cells expressing the beta-cell specific hormone INS are identified by nuclear localized H2B-Cherry reporter upon pancreatic endocrine differentiation. Thus, the generated reporter hiPSCs enable live identification of INS hormone-producing beta-like cells. AU - Blöchinger, A. AU - Siehler, J. AU - Wißmiller, K. AU - Shahryari, A. AU - Burtscher, I. AU - Lickert, H. C1 - 59004 C2 - 48518 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of an INSULIN-H2B-Cherry reporter human iPSC line. JO - Stem Cell Res. VL - 45 PB - Elsevier PY - 2020 SN - 1873-5061 ER - TY - JOUR AB - The aristaless related homeobox (ARX) transcription factor plays a crucial role in glucagon-producing alpha-cell differentiation. Here, we generate an ARX reporter iPSC line by 3' fusion of an intervening viral T2A sequence followed by a nuclear-localized histone 2B-cyan fluorescent protein (nCFP). The resulting cells have a normal karyotype and preserved pluripotency. In vitro differentiation of the ARX(nCFP/nCFP) reporter iPSCs towards the endocrine lineage confirmed the specific co-expression of the reporter protein in human glucagon' alpha-like cells. Thus, ARX(nCFP/nCFP) iPSC line will provide a powerful tool to monitor human a-cell progenitor differentiation as well as ARX(+) alpha-like cell function in vitro. AU - Moya, N. AU - Shahryari, A. AU - Burtscher, I. AU - Beckenbauer, J. AU - Bakhti, M. AU - Lickert, H. C1 - 59438 C2 - 48814 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of a homozygous ARX nuclear CFP (ARX(nCFP/nCFP)) reporter human iPSC line (HMGUi001-A-4). JO - Stem Cell Res. VL - 46 PB - Elsevier PY - 2020 SN - 1873-5061 ER - TY - JOUR AB - The INK4 locus is considered as a hot-spot region for the complex genetic disorders, including cancer, type 2 diabetes (T2D) and coronary artery disease (CAD). By CRISPR/Cas9 gene editing, we generated a human induced pluripotent stem cell (hiPSC) line (HMGUi001-A-5) deleting an 8 kb genomic DNA encompassing six T2D-associated SNPs at the INK4 locus. The resulting hiPSC line revealed a normal karyotype, preserved pluripotency and was able to differentiate towards germ layers, endoderm, mesoderm and ectoderm. Thus, the HMGUi001-A-5 line could provide a valuable cellular model to explore the molecular mechanisms linking these SNPs to T2D and other genetic disorders. AU - Shahryaria, A. AU - Moya, N. AU - Siehler, J. AU - Wang, X. AU - Blöchinger, A. AU - Burtscher, I. AU - Bakhti, M. AU - Mowla, S.J.* AU - Lickert, H. C1 - 59837 C2 - 49065 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of a human iPSC line harboring a biallelic large deletion at the INK4 locus (HMGUi001-A-5). JO - Stem Cell Res. VL - 47 PB - Elsevier PY - 2020 SN - 1873-5061 ER - TY - JOUR AB - Induced pluripotent stem cells (iPSCs) can be used to generate different somatic cell types in vitro, including insulin-producing pancreatic beta-cells. Here, we have generated iPSCs from a healthy male individual using an episomal reprogramming method. The resulting iPSCs are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Furthermore, we show that this iPSC line can be differentiated into pancreatic lineage cells. Taken together, this iPSC line will be useful to test differentiation protocols towards beta-cell as well as other cell types and will also serve as a control for drug development and disease modelling studies. AU - Wang, X. AU - Malinowski, A.R. AU - Beckenbauer, J. AU - Siehler, J. AU - Blöchinger, A. AU - Meitinger, T. AU - Häring, H.-U. AU - Staiger, H. AU - Burtscher, I. AU - Lickert, H. C1 - 56760 C2 - 47381 CY - Radarweg 29, 1043 Nx Amsterdam, Netherlands TI - Generation of a human induced pluripotent stem cell line (HMGUi002-A) from a healthy male individual. JO - Stem Cell Res. VL - 39 PB - Elsevier PY - 2019 SN - 1873-5061 ER - TY - JOUR AB - Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associatedwithMaturity-Onset Diabetes of the Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a C18R heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 C18R iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms. AU - Wang, X. AU - Chen, S.* AU - Burtscher, I. AU - Sterr, M. AU - Hieronimus, A. AU - Machicao, F. AU - Staiger, H. AU - Häring, H.-U. AU - Lederer, G.* AU - Meitinger, T. AU - Lickert, H. C1 - 50281 C2 - 42251 CY - Amsterdam SP - 292-295 TI - Generation of a human induced pluripotent stem cell (iPSC) line from a patient with family history of diabetes carrying a C18R mutation in the PDX1 gene. JO - Stem Cell Res. VL - 17 IS - 2 PB - Elsevier Science Bv PY - 2016 SN - 1873-5061 ER - TY - JOUR AB - Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor PDX1 leads to pancreatic agenesis, whereas certain heterozygous point mutations are associated with Maturity-Onset Diabetes of the Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a P33T heterozygous mutation in the transactivation domain of PDX1. The resulting PDX1 P33T iPSCs generated by episomal reprogramming are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Taken together, this iPSC line will be useful to study diabetes pathomechanisms. AU - Wang, X. AU - Chen, S.* AU - Burtscher, I. AU - Sterr, M. AU - Hieronimus, A. AU - Machicao, F. AU - Staiger, H. AU - Häring, H.-U. AU - Lederer, G.* AU - Meitinger, T. AU - Lickert, H. C1 - 50282 C2 - 42250 CY - Amsterdam SP - 273-276 TI - Generation of a human induced pluripotent stem cell (iPSC) line from a patient carrying a P33T mutation in the PDX1 gene. JO - Stem Cell Res. VL - 17 IS - 2 PB - Elsevier Science Bv PY - 2016 SN - 1873-5061 ER - TY - JOUR AB - Human embryonic stem (ES) cells can undergo spontaneously differentiation in standard culture conditions, demonstrating that the undifferentiated state is relatively unstable. The heterogeneous expression of SSEA3 observed within human ES colonies, provides a means to examine undifferentiated stem cell substates. Through functional testing of single cells we have shown that undifferentiated ES cells can be segregated into functionally discrete subpopulations on the basis of SSEA3 expression: SSEA3(High), SSEA(Low) and SSEA3(Negative). Human ES subpopulations were found to be interconvertible, but they possess distinct properties when challenged to differentiate along the neural lineage. These data suggest that ES cells with pluripotent/self-renewal capacities can exhibit different responses to induction of differentiation. AU - Tonge, P.D.* AU - Shigeta, M. AU - Schroeder, T. AU - Andrews, P.W.* C1 - 6746 C2 - 29202 CY - Kidlington, Oxford SP - 145-153 TI - Functionally defined substates within the human embryonic stem cell compartment. JO - Stem Cell Res. VL - 7 IS - 2 PB - Elsevier PY - 2011 SN - 1873-5061 ER -