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

Tatyana Grinenko (), Anne Eugster, Lars Thielecke, Beáta Ramasz, Anja Krüger, Sevina Dietz, Ingmar Glauche, Alexander Gerbaulet, Malte Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis and Ben Wielockx ()
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Tatyana Grinenko: Technische Universität Dresden
Anne Eugster: Technische Universität Dresden
Lars Thielecke: Technische Universität Dresden
Beáta Ramasz: Technische Universität Dresden
Anja Krüger: Technische Universität Dresden
Sevina Dietz: Technische Universität Dresden
Ingmar Glauche: Technische Universität Dresden
Alexander Gerbaulet: Technische Universität Dresden
Malte Bonin: Technische Universität Dresden
Onur Basak: Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht
Hans Clevers: Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht
Triantafyllos Chavakis: Technische Universität Dresden
Ben Wielockx: Technische Universität Dresden

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04188-7

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