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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.

Original publication

DOI

10.1084/jem.20131189

Type

Journal article

Journal

J Exp Med

Publication Date

10/02/2014

Volume

211

Pages

181 - 188

Keywords

Animals, Cell Lineage, Colony-Forming Units Assay, Erythroid Precursor Cells, Erythropoiesis, Erythropoietin, Gene Expression Profiling, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Mice, Mice, Congenic, Mice, Inbred C57BL, Mice, Transgenic, Multipotent Stem Cells, Recombinant Proteins