Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate.
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.
Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, England, UK.
Amit
A
Grover
Elena
E
Mancini
Susan
S
Moore
Adam J
AJ
Mead
Deborah
D
Atkinson
Kasper D
KD
Rasmussen
Donal
D
O'Carroll
Sten Eirik W
SE
Jacobsen
Claus
C
Nerlov
D000818:Animals; D019070:Cell Lineage; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D004921:Erythropoietin