Journal Article

Human haematopoietic stem cell lineage commitment is a continuous process

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

2017

Overview

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. Velten et al.  use single-cell transcriptomics and functional data to map the early lineage commitment of human haematopoietic stem cells as a continuous process of cells passing through transitory states rather than demarcating discrete progenitors.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/100 / 45/91 / 631/136/1660/1986 / 631/532 / 631/532/1360 / 631/532/2118/1542 / Adult / Animals / Antigens, CD - metabolism / Blood cancer / Branches / Cancer Research / Cell Biology / Cell development (Biology) / Cell lineage / Cell Lineage - genetics / Cell Proliferation - genetics / Cells (biology) / Combinatorial analysis / Cytological research / Developmental Biology / Differentiation / Female / Flow cytometry / Gene expression / Gene Regulatory Networks / Health aspects / Hematopoiesis / Hematopoiesis - genetics / Hematopoietic stem cells / Hematopoietic Stem Cells - cytology / Hematopoietic Stem Cells - metabolism / Homeostasis / Humans / Life Sciences / Male / Mice / Models, Biological / Modules / Multipotent Stem Cells - cytology / Multipotent Stem Cells - metabolism / Physiological aspects / Populations / Priming / Stem Cells / Transcriptome - genetics