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EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis.

Daniel HidalgoBejder JacobRamona PopKyle J GellatlyYung HwangS Maxwell ScalfAnna E EastmanJane-Jane ChenJulie Lihua ZhuJules A A C HeubergerShangqin GuoMark J KouryNikolai Baastrup NordsborgMerav Socolovsky
Published in: Nature communications (2021)
The erythroid terminal differentiation program couples sequential cell divisions with progressive reductions in cell size. The erythropoietin receptor (EpoR) is essential for erythroblast survival, but its other functions are not well characterized. Here we use Epor -/- mouse erythroblasts endowed with survival signaling to identify novel non-redundant EpoR functions. We find that, paradoxically, EpoR signaling increases red cell size while also increasing the number and speed of erythroblast cell cycles. EpoR-regulation of cell size is independent of established red cell size regulation by iron. High erythropoietin (Epo) increases red cell size in wild-type mice and in human volunteers. The increase in mean corpuscular volume (MCV) outlasts the duration of Epo treatment and is not the result of increased reticulocyte number. Our work shows that EpoR signaling alters the relationship between cycling and cell size. Further, diagnostic interpretations of increased MCV should now include high Epo levels and hypoxic stress.
Keyphrases
  • single cell
  • cell therapy
  • type diabetes
  • adipose tissue
  • bone marrow
  • skeletal muscle
  • cell death
  • induced apoptosis
  • endoplasmic reticulum stress
  • induced pluripotent stem cells