EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis. / Hidalgo, Daniel; Bejder, Jacob; Pop, Ramona; Gellatly, Kyle; Hwang, Yung; Scalf, S Maxwell; Eastman, Anna E; Chen, Jane-Jane; Zhu, Lihua Julie; Heuberger, Jules A A C; Guo, Shangqin; Koury, Mark J; Nordsborg, Nikolai Baastrup; Socolovsky, Merav.
In: Nature Communications, Vol. 12, 7334, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis
AU - Hidalgo, Daniel
AU - Bejder, Jacob
AU - Pop, Ramona
AU - Gellatly, Kyle
AU - Hwang, Yung
AU - Scalf, S Maxwell
AU - Eastman, Anna E
AU - Chen, Jane-Jane
AU - Zhu, Lihua Julie
AU - Heuberger, Jules A A C
AU - Guo, Shangqin
AU - Koury, Mark J
AU - Nordsborg, Nikolai Baastrup
AU - Socolovsky, Merav
N1 - © 2021. The Author(s).
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Faculty of Science
KW - Erythropoietin receptor
KW - EpoR
KW - EpoR signaling
KW - Mean corpuscular volume (MCV)
U2 - 10.1038/s41467-021-27562-4
DO - 10.1038/s41467-021-27562-4
M3 - Journal article
C2 - 34921133
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7334
ER -
ID: 287691579