Human haematopoietic stem cell lineage commitment is a continuous process

被引：604

作者：

Velten, Lars ^{[1
]}

Haas, Simon F. ^{[2
,3
,4
]}

Raffel, Simon ^{[2
,4
,5
]}

Blaszkiewicz, Sandra ^{[2
,3
]}

Islam, Saiful ^{[7
]}

Hennig, Bianca P. ^{[1
]}

Hirche, Christoph

Lutz, Christoph ^{[5
,6
]}

Buss, Eike C.

Nowak, Daniel ^{[8
]}

Boch, Tobias

Hofmann, Wolf-Karsten

Ho, Anthony D. ^{[6
]}

Huber, Wolfgang

Trumpp, Andreas ^{[3
,4
,5
,9
]}

Essers, Marieke A. G. ^{[1
,2
]}

Steinmetz, Lars M. ^{[7
,10
]}

机构：

[1] EMBL, Genome Biol Unit, D-69117 Heidelberg, Germany

[2] Heidelberg Inst Stem Cell Technol & Expt Med HI S, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Div Stem Cells & Canc, Haematopoiet Stem Cells & Stress Grp, D-69120 Heidelberg, Germany

[4] German Canc Res Ctr, Div Stem Cells & Canc, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany

[6] Heidelberg Univ, Dept Internal Med 5, D-69120 Heidelberg, Germany

[7] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[8] Heidelberg Univ, Med Fac Mannheim, Dept Hematol & Oncol, D-68167 Mannheim, Germany

[9] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[10] Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

来源：

NATURE CELL BIOLOGY | 2017年 / 19卷 / 04期

基金：

美国国家卫生研究院;

关键词：

RNA-SEQ; NONGENETIC HETEROGENEITY; SELF-RENEWAL; PROGENITORS; IDENTIFICATION; GRANULOCYTE; MAINTENANCE; DYNAMICS; TISSUES; MARROW;

D O I：

10.1038/ncb3493

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：271 / +

页数：23

共 59 条

[1] Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment [J].