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Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate.


ABSTRACT: The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type.

SUBMITTER: Grover A 

PROVIDER: S-EPMC3920567 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate.

Grover Amit A   Mancini Elena E   Moore Susan S   Mead Adam J AJ   Atkinson Deborah D   Rasmussen Kasper D KD   O'Carroll Donal D   Jacobsen Sten Eirik W SE   Nerlov Claus C  

The Journal of experimental medicine 20140203 2


The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to  ...[more]

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