Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice

Nature Communications
Tatyana GrinenkoBen Wielockx

Abstract

Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle. Additionally, the phenotype of the undivided but differentiated progenitors correlated with the expression of lineage-specific genes and loss of multipotency. Thus HSC fate decisions can be uncoupled from physical cell division. These results facilitate a better understanding of the mechanisms that control fate decisions in hematopoietic cells.

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Citations

Jul 25, 2018·International Journal of Molecular Sciences·Geoffrey BrownPanagiotis Tsapogas
May 20, 2020·Current Opinion in Hematology·Marjorie Brand, Edward Morrissey
Nov 25, 2020·Journal of Hematology & Oncology·Lei ZhangJiwang Zhang
Dec 18, 2020·Frontiers in Immunology·Weinian LiaoJunping Wang
May 1, 2021·Cells·Tyler J WildesCatherine T Flores
Jun 2, 2021·Current Opinion in Hematology·Dirk Loeffler, Timm Schroeder
Jul 25, 2021·International Journal of Molecular Sciences·Hyun-Jun ParkSeong-Hyop Kim
Dec 24, 2018·Journal of Theoretical Biology·Nils B BeckerThomas Höfer
Dec 23, 2021·Advanced Healthcare Materials·Aidan E Gilchrist, Brendan A C Harley

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Methods Mentioned

BETA
PCR
single-cell sequencing
fluorescence-activated cell sorter
FACS

Software Mentioned

Fluidigm Real - Time PCR
Prism
R
KNIME
R package “ stats ”
GraphPad
FACS
RStudio

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