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Human haematopoietic stem cell lineage commitment is a continuous process

Item Type:Article
Title:Human haematopoietic stem cell lineage commitment is a continuous process
Creators Name:Velten, L. and Haas, S.F. and Raffel, S. and Blaszkiewicz, S. and Islam, S. and Hennig, B.P. and Hirche, C. and Lutz, C. and Buss, E.C. and Nowak, D. and Boch, T. and Hofmann, W.K. and Ho, A.D. and Huber, W. and Trumpp, A. and Essers, M.A.G. and Steinmetz, L.M.
Abstract:Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations. Instead, unilineage-restricted cells emerge directly from a 'continuum of low-primed undifferentiated haematopoietic stem and progenitor cells' (CLOUD-HSPCs). Distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of haematopoiesis. These data reveal a continuous landscape of human steady-state haematopoiesis downstream of HSCs and provide a basis for the understanding of haematopoietic malignancies.
Keywords:Biological Models, CD Antigens, Cell Lineage, Cell Proliferation, Gene Regulatory Networks, Hematopoiesis, Hematopoietic Stem Cells, Multipotent Stem Cells, Transcriptome, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:271-281
Date:April 2017
Official Publication:https://doi.org/10.1038/ncb3493
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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