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 von Bonin; Onur Basak; Hans Clevers; Triantafyllos Chavakis; Ben Wielockx

doi:10.1038/s41467-018-04188-7

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 von Bonin, Onur Basak, Hans Clevers, Triantafyllos Chavakis, Ben Wielockx

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

60 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1898
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04188-7
Publication status	Published - 15 May 2018

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title = "Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice",

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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doi = "10.1038/s41467-018-04188-7",

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T1 - Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice

AU - Grinenko, Tatyana

AU - Eugster, Anne

AU - Thielecke, Lars

AU - Ramasz, Beáta

AU - Krüger, Anja

AU - Dietz, Sevina

AU - Glauche, Ingmar

AU - Gerbaulet, Alexander

AU - von Bonin, Malte

AU - Basak, Onur

AU - Clevers, Hans

AU - Chavakis, Triantafyllos

AU - Wielockx, Ben

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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.

AB - 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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DO - 10.1038/s41467-018-04188-7

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SN - 2041-1723

VL - 9

SP - 1898

JO - Nature Communications

JF - Nature Communications

IS - 1

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

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