Li Xiaohong, Dong Yong, Pan Xu, Sun Wencui, Xue Yuan, Zhou Ya, Lai Mowen, Zhang Yonggang, Ma Feng
Center for Stem Cell Research and Application, Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China.
School of Basic Medicine, Chengdu Medical College, Chengdu 610500, China.
J Mol Cell Biol. 2025 Jun 12;16(12). doi: 10.1093/jmcb/mjae057.
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.
在定向分化为红系细胞谱系之前，造血干细胞沿着髓系细胞途径分化，在骨髓中生成巨核-红系双潜能祖细胞。最近的研究表明，红系祖细胞（EryP）可能在常见髓系祖细胞（CMP）水平产生。然而，由于缺乏合适的标志物，对于这些定向EryP细胞在CMP发育过程中的早期分化了解甚少。在此，我们使用miR-144/451-eGFP基因敲入小鼠，发现定向红系细胞的早期分化可以通过CMP中miR-144/451的表达来定义。单细胞RNA测序显示，miR-144/451+祖细胞表现出明显的红系谱系细胞分化特征，并与巨核细胞和其他髓系细胞谱系不同。这些祖细胞在体外和体内均专门分化为红系细胞，并且向红系细胞谱系的定向分化伴随着CD53表达的丧失。我们的研究结果将有助于进一步了解红系发育的分子机制，并支持鉴定与红细胞发育相关疾病的治疗靶点。
