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人类造血干细胞谱系定向分化是一个连续的过程。

Human haematopoietic stem cell lineage commitment is a continuous process.

作者信息

Velten Lars, Haas Simon F, Raffel Simon, Blaszkiewicz Sandra, Islam Saiful, Hennig Bianca P, Hirche Christoph, Lutz Christoph, Buss Eike C, Nowak Daniel, Boch Tobias, Hofmann Wolf-Karsten, Ho Anthony D, Huber Wolfgang, Trumpp Andreas, Essers Marieke A G, Steinmetz Lars M

机构信息

European Molecular Biology Laboratory (EMBL), Genome Biology Unit, 69117 Heidelberg, Germany.

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.

出版信息

Nat Cell Biol. 2017 Apr;19(4):271-281. doi: 10.1038/ncb3493. Epub 2017 Mar 20.

DOI:10.1038/ncb3493
PMID:28319093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5496982/
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.

摘要

人们认为，造血过程是通过造血干细胞（HSCs）按照寡能、双能和单能祖细胞的树状层次逐步发展而来的。然而，该模型是基于对预先定义的流式分选细胞群体的分析。在这里，我们以单细胞分辨率整合了流式细胞术、转录组学和功能数据，以定量描绘人类造血干细胞向谱系定向分化的早期过程。在稳态过程中，单个造血干细胞沿着多个方向逐渐获得谱系偏向，而不经过离散的分层组织的祖细胞群体。相反，单谱系受限细胞直接从“低预激发未分化造血干细胞和祖细胞连续体”（CLOUD-HSPCs）中产生。不同的基因表达模块以组合方式发挥作用，以控制干性、早期谱系预激发以及随后向造血所有主要分支的进展。这些数据揭示了造血干细胞下游人类稳态造血的连续图景，并为理解造血系统恶性肿瘤提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6baf/5496982/fbe1c81b7a09/nihms854264f8.jpg
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