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- Title
EVA1A regulates hematopoietic stem cell regeneration via ER-mitochondria mediated apoptosis.
- Authors
Liu, Bo; Zhou, Yuanyuan; Wu, Qiaofeng; Fu, Yuting; Zhang, Xianli; Wang, Zhenkun; Yi, Weiwei; Wang, Hu; Chen, Zhiyang; Song, Zhangfa; Xiong, Wei; Qiu, Yugang; He, Weifeng; Ju, Zhenyu
- Abstract
Excessive protein synthesis upon enhanced cell proliferation frequently results in an increase of unfolded or misfolded proteins. During hematopoietic regeneration, to replenish the hematopoietic system, hematopoietic stem cells (HSCs) are activated and undergo a rapid proliferation. But how the activated HSCs respond to the proliferation pressure is still ambiguous; The proper control of the functional reservoir in the activated HSCs remains poorly understood. Here, we show a significant upregulation of EVA1A protein associated with the increase of ER stress during hematopoietic regeneration. Deletion of Eva1a significantly enhances the regeneration capacity of HSCs by inhibiting the ER stress-induced apoptosis. Mechanistically, the expression of EVA1A protein was upregulated by CHOP, and thereby promoted the ER-mitochondria interlinking via MCL1, which resulted in mitochondria-mediated apoptosis. These findings reveal a pathway for ER stress responses of HSCs by the EVA1A mediated apoptosis, which play an important role in HSCs regeneration.
- Publication
Cell Death & Disease, 2023, Vol 14, Issue 1, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-023-05559-9