Human Haematopoietic Stem Cell Lineage Commitment is a Continuous Process

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2017 Mar 21

PMID 28319093

Citations 441

Authors

Lars Velten

Simon F Haas

Simon Raffel

Sandra Blaszkiewicz

Saiful Islam

Bianca P Hennig

Christoph Hirche

Christoph Lutz

Eike C Buss

Daniel Nowak

Tobias Boch

Wolf-Karsten Hofmann

Anthony D Ho

Wolfgang Huber

Andreas Trumpp

Marieke A G Essers

Lars M Steinmetz

Affiliations

Soon will be listed here.

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.

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