| Title: |
The Erythropoietin Receptor Stimulates Rapid Cycling and Formation of Larger Red Cells During Mouse and Human Erythropoiesis [preprint] |
| Authors: |
Hidalgo, Daniel; Bejder, Jacob; Pop, Ramona; 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 |
| Contributors: |
Morningside Graduate School of Biomedical Sciences; Department of Molecular, Cell and Cancer Biology |
| Source: |
bioRxiv |
| Publication Year: |
2022 |
| Collection: |
University of Massachusetts, Medical School: eScholarship@UMMS |
| Subject Terms: |
Developmental Biology; Erythropoiesis; Cell Biology |
| Description: |
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review. The PDF available for download is Version 2 of this preprint. The complete version history of this preprint is available at bioRxiv. ; Erythroid terminal differentiation entails cell divisions that are coupled to progressive decreases in cell size. EpoR signaling is essential for the survival of erythroid precursors, but it is unclear whether it has other functions in these cells. Here we endowed mouse precursors that lack the EpoR with survival signaling, finding that this was sufficient to support their differentiation into enucleated red cells, but that the process was abnormal. Precursors underwent fewer and slower cell cycles and yet differentiated into smaller red cells. Surprisingly, EpoR further accelerated cycling of early erythroblasts, the fastest cycling cells in the bone marrow, while simultaneously increasing their cell size. EpoR-mediated formation of larger red cells was independent of the established pathway regulating red cell size by iron through Heme-regulated eIF2α kinase (HRI). We confirmed the effect of Epo on red cell size in human volunteers, whose mean corpuscular volume (MCV) increased following Epo administration. This increase persisted after Epo declined and was not the result of increased reticulocytes. Our work reveals a unique effect of EpoR signaling on the interaction between the cell cycle and cell growth. Further, it suggests new diagnostic interpretations for increased red cell volume, as reflecting high Epo and erythropoietic stress. ; Bioinformatics and Computational Biology |
| Document Type: |
report |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Now published in Nature Communications, doi:https://doi.org/10.1038/s41467-021-27562-4; bioRxiv 2020.11.30.404780; doi: https://doi.org/10.1101/2020.11.30.404780. Link to preprint on bioRxiv.; http://hdl.handle.net/20.500.14038/29621; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2870&context=faculty_pubs&unstamped=1; https://escholarship.umassmed.edu/faculty_pubs/1839; faculty_pubs/1839 |
| DOI: |
10.1101/2020.11.30.404780 |
| Availability: |
https://doi.org/10.1101/2020.11.30.404780; https://hdl.handle.net/20.500.14038/29621; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2870&context=faculty_pubs&unstamped=1; https://escholarship.umassmed.edu/faculty_pubs/1839 |
| Rights: |
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.D0B1F433 |
| Database: |
BASE |