Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells.
Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells.
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DOI：
10.1016/j.celrep.2023.113308
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发表时间：
2023-10
期刊：
影响因子：
8.8
通讯作者：
Youwei Chen;Ying Chen;Qianyan Li;Huahua Liu;Jiazhen Han;Hailin Zhang;Liming Cheng;Gufa Lin-Gufa
中科院分区：
文献类型：
--
作者：
Youwei Chen;Ying Chen;Qianyan Li;Huahua Liu;Jiazhen Han;Hailin Zhang;Liming Cheng;Gufa Lin-Gufa
RNA结合蛋白Musashi-1（MSI 1）调节成体干细胞的增殖和分化。然而，它在胚胎干细胞（ESCs）和早期胚胎发育中的作用仍然知之甚少。在这里，我们报告的存在下，短的C-末端MSI 1（MSI 1-C）蛋白在早期小鼠胚胎和小鼠胚胎干细胞，但不是在人类胚胎干细胞，在传统的培养条件。在小鼠胚胎和mESC中，MSI 1-C的缺失与全长MSI 1一起导致早期胚胎发育停滞和多能性溶解。MSI 1-C在幼稚诱导后被诱导，并促进hESC幼稚多能性获得，将致敏的hESC的多能性提高至形成样状态。MSI 1-C蛋白定位于细胞核，与参与DNA损伤修复的RNA（包括MLH 1、BRCA 1和MSH 2）结合，使hESC在人-小鼠种间细胞竞争中存活更好，并延长形成胚状体的能力。这项研究确定MSI 1-C作为ESC多能性状态和早期胚胎发育的重要调节因子。
The RNA-binding protein Musashi-1 (MSI1) regulates the proliferation and differentiation of adult stem cells. However, its role in embryonic stem cells (ESCs) and early embryonic development remains poorly understood. Here, we report the presence of short C-terminal MSI1 (MSI1-C) proteins in early mouse embryos and mouse ESCs, but not in human ESCs, under conventional culture conditions. In mouse embryos and mESCs, deletion of MSI1-C together with full-length MSI1 causes early embryonic developmental arrest and pluripotency dissolution. MSI1-C is induced upon naive induction and facilitates hESC naive pluripotency acquisition, elevating the pluripotency of primed hESCs toward a formative-like state. MSI1-C proteins are nuclear localized and bind to RNAs involved in DNA-damage repair (includingMLH1,BRCA1, andMSH2), conferring on hESCs better survival in human-mouse interspecies cell competition and prolonged ability to form blastoids. This study identifies MSI1-C as an essential regulator in ESC pluripotency states and early embryonic development.