Academic Journal
Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells
| Title: | Overexpression of miR-99a promoted expansion and suppressed differentiation of hematopoietic stem/progenitor cells |
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| Authors: | Wenjun Wang, Xing Hao, Xue Lv, Yihan Li, Wen Xing, Ting Chen, Xiaohui Si, Jun Shi, Yuan Zhou |
| Source: | Scientific Reports, Vol 15, Iss 1, Pp 1-15 (2025) |
| Publisher Information: | Nature Portfolio, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | miR-99a, Hematopoietic stem/progenitor cells, Proliferation, Differentiation, NIPBL, Medicine, Science |
| More Details: | Abstract MicroRNAs (miRNAs) are a class of non-coding RNAs involved in a variety of pathophysiological processes. We have previously reported that the abnormally high expression of miR-99a is associated with drug resistance and poor prognosis in acute myeloid leukemia. However, the impact of miR-99a on normal hematopoiesis is not well understood. To investigate the effect of aberrant miR-99a overexpression on hematopoietic stem and progenitor cells (HSPCs), we overexpressed miR-99a in human umbilical cord blood CD34+ cells. We observed that miR-99a overexpression increased the proliferation, self-renewal capacity, and transplantation efficiency of HSPCs with or without a clonal hematopoiesis-associated mutation (JAK2 V617F). Meanwhile, we found that overexpression of miR-99a blocked the maturation and differentiation of granulocytes/monocytes and erythrocytes. We then identified NIPBL as a direct target of miR-99a. NIPBL knockdown in HSPCs showed a phenotype similar to miR-99a overexpression. In this study, we elucidate that abnormally high expression of miR-99a can enhance the proliferative capacity of HSPCs but inhibit myeloid differentiation and maturation. Taken together, our work has uncovered important roles for miR-99a in regulating HSPCs by enhancing the proliferation and self-renewal capacity of HSPCs but inhibiting differentiation, which play important roles in leukemic transformation. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-025-92827-7 |
| Access URL: | https://doaj.org/article/0183a1eb1a8b4814947ef9ec4a5c8352 |
| Accession Number: | edsdoj.0183a1eb1a8b4814947ef9ec4a5c8352 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-025-92827-7 |
| Published in: | Scientific Reports |
| Language: | English |