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Early differentiation of committed erythroid cells defined by miR-144/451 expression
Xiaohong Li1 , Yong Dong2 , Xu Pan1 , Wencui Sun1 , Yuan Xue1 , Ya Zhou1 , Mowen Lai1 , Yonggang Zhang1,* , Feng Ma1,*
1Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China
2School of Basic Medicine, Chengdu Medical College, Chengdu 610500, China
*Correspondence to:Yonggang Zhang , Email:yonggangzhang@ibt.pumc.edu.cn Feng Ma , Email:mafeng@ibt.pumc.edu.cn
J Mol Cell Biol, Volume 16, Issue 12, December 2024, mjae057,  https://doi.org/10.1093/jmcb/mjae057
Keyword: erythroid progenitor cell, miR-144/451, common myeloid progenitor, erythropoiesis, megakaryocyte, single-cell RNA sequencing

Before committing to an erythroid cell lineage, hematopoietic stem cells differentiate along a myeloid cell pathway to generate megakaryocyte–erythroid biopotential progenitor cells in bone marrow. Recent studies suggest that erythroid progenitors (EryPs) could be generated at the level of common myeloid progenitors (CMPs). However, due to a lack of suitable markers, little is known about the early differentiation of these committed EryP cells during CMP development. Herein, using miR-144/451-eGFP knock-in mice, we found that early differentiation of committed erythroid cells could be defined by miR-144/451 expression within CMPs. Single-cell RNA sequencing showed that miR-144/451+ progenitors show obvious differentiation characteristics of erythroid lineage cells and diverge from megakaryocyte and other myeloid cell lineages. These progenitors exclusively give rise to erythroid cells, both in vitro and in vivo, and the commitment to an erythroid cell lineage is accompanied by loss of CD53 expression. Our findings will facilitate further understanding of the molecular mechanisms governing erythroid development and support the identification of therapeutic targets for diseases related to erythrocyte development.