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MicroRNA-21 maintains hematopoietic stem cell homeostasis through sustaining the nuclear factor-B signaling pathway in mice

Long-term hematopoietic output is dependent on hematopoietic stem cell (HSC) homeostasis which is maintained by a complex molecular network in which microRNA play crucial roles, although the underlying molecular basis has not been fully elucidated. Here we show that microRNA-21 (miR-21) is enriched...

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Detalles Bibliográficos
Autores principales: Hu, Mengjia, Lu, Yukai, Zeng, Hao, Zhang, Zihao, Chen, Shilei, Qi, Yan, Xu, Yang, Chen, Fang, Tang, Yong, Chen, Mo, Du, Changhong, Shen, Mingqiang, Wang, Fengchao, Su, Yongping, Wang, Song, Wang, Junping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849563/
https://www.ncbi.nlm.nih.gov/pubmed/31974197
http://dx.doi.org/10.3324/haematol.2019.236927
Descripción
Sumario:Long-term hematopoietic output is dependent on hematopoietic stem cell (HSC) homeostasis which is maintained by a complex molecular network in which microRNA play crucial roles, although the underlying molecular basis has not been fully elucidated. Here we show that microRNA-21 (miR-21) is enriched in murine HSC, and that mice with conditional knockout of miR-21 exhibit an obvious perturbation in hematopoiesis. Moreover, significant loss of HSC quiescence and long-term reconstituting ability are observed in the absence of miR-21. Further studies revealed that miR-21 deficiency markedly decreases the nuclear factor kappa B (NF-B) pathway, accompanied by increased expression of PDCD4, a direct target of miR-21, in HSC. Interestingly, overexpression of PDCD4 in wild-type HSC generates similar phenotypes as those of miR-21-deficient HSC. More importantly, knockdown of PDCD4 can significantly rescue the attenuation of NF-B activity, thereby improving the defects in miR-21-null HSC. On the other hand, we found that miR-21 is capable of preventing HSC from ionizing radiation- induced DNA damage via activation of the NF-B pathway. Collectively, our data demonstrate that miR-21 is involved in maintaining HSC homeostasis and function, at least in part, by regulating the PDCD4-mediated NF-B pathway and provide a new insight into radioprotection of HSC.