Human haematopoietic stem cell lineage commitment is a continuous process.

Autor: Velten L; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany., Haas SF; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer, Haematopoietic Stem Cells and Stress Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer and DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Raffel S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer and DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany., Blaszkiewicz S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer, Haematopoietic Stem Cells and Stress Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Islam S; Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA., Hennig BP; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany., Hirche C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer, Haematopoietic Stem Cells and Stress Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Lutz C; Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany., Buss EC; Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany., Nowak D; Department of Hematology and Oncology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany., Boch T; Department of Hematology and Oncology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany., Hofmann WK; Department of Hematology and Oncology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany., Ho AD; Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, Germany., Huber W; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany., Trumpp A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer and DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Essers MA; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.; Division of Stem Cells and Cancer, Haematopoietic Stem Cells and Stress Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Steinmetz LM; European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.; Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.; Stanford Genome Technology Center, Palo Alto, California 94304, USA.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2017 Apr; Vol. 19 (4), pp. 271-281. Date of Electronic Publication: 2017 Mar 20.
DOI: 10.1038/ncb3493
Abstrakt: 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.
Databáze: MEDLINE
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