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J Exp Med. 2018 Nov 5;215(11):2815-2832. doi: 10.1084/jem.20180136. Epub 2018 Oct 5.

Kinetics of adult hematopoietic stem cell differentiation in vivo.

Author information

1
Department of Pathology, New York University School of Medicine, New York, NY.
2
Graduate Program in Pathobiology and Molecular Medicine, Columbia University Medical Center, New York, NY.
3
Center for Genomics and Systems Biology, New York University, New York, NY.
4
New York Genome Center, New York, NY.
5
Department of Pathology, New York University School of Medicine, New York, NY Boris.Reizis@nyumc.org.

Abstract

Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.

PMID:
30291161
PMCID:
PMC6219744
[Available on 2019-05-05]
DOI:
10.1084/jem.20180136

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