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Hoppe, P.S. ; Schwarzfischer, M. ; Loeffler, D. ; Kokkaliaris, K.D. ; Hilsenbeck, O. ; Moritz, N. ; Endele, M. ; Filipczyk, A. ; Gambardella, A.* ; Ahmed, N.* ; Etzrodt, M.* ; Coutu, D.L.* ; Rieger, M.A. ; Marr, C. ; Strasser, M. ; Schauberger, B. ; Burtscher, I. ; Ermakova, O.* ; Bürger, A. ; Lickert, H. ; Nerlov, C.* ; Theis, F.J. ; Schroeder, T.

Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios.

Nature 535, 299-302 (2016)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The mechanisms underlying haematopoietic lineage decisions remain disputed. Lineage-affiliated transcription factors with the capacity for lineage reprogramming, positive auto-regulation and mutual inhibition have been described as being expressed in uncommitted cell populations. This led to the assumption that lineage choice is cell-intrinsically initiated and determined by stochastic switches of randomly fluctuating cross-antagonistic transcription factors. However, this hypothesis was developed on the basis of RNA expression data from snapshot and/or population-averaged analyses. Alternative models of lineage choice therefore cannot be excluded. Here we use novel reporter mouse lines and live imaging for continuous single-cell long-term quantification of the transcription factors GATA1 and PU.1 (also known as SPI1). We analyse individual haematopoietic stem cells throughout differentiation into megakaryocytic-erythroid and granulocytic-monocytic lineages. The observed expression dynamics are incompatible with the assumption that stochastic switching between PU.1 and GATA1 precedes and initiates megakaryocytic-erythroid versus granulocytic-monocytic lineage decision-making. Rather, our findings suggest that these transcription factors are only executing and reinforcing lineage choice once made. These results challenge the current prevailing model of early myeloid lineage choice.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Transcription Factor Gata-1; Hematopoietic Stem-cells; Progenitor Cells; Erythroid-differentiation; Multipotent Progenitors; Transgenic Mice; Commitment; Specification; Activation; Expression
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 535, Heft: 7611, Seiten: 299-302 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
Institute of Computational Biology (ICB)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Developmental Genetics (IDG)
POF Topic(s) 30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
30201 - Metabolic Health
Forschungsfeld(er) Stem Cell and Neuroscience
Enabling and Novel Technologies
Helmholtz Diabetes Center
Genetics and Epidemiology
PSP-Element(e) G-500800-001
G-503800-001
G-502300-001
G-500500-001
DOI 10.1038/nature18320
WOS ID WOS:000379912600060
Scopus ID 84978698935
PubMed ID 27411635
Erfassungsdatum 2016-07-20
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