TASOR expression in naive embryonic stem cells safeguards their developmental potential.

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-10-24 DOI:10.1016/j.celrep.2024.114887

Carlos A Pinzon-Arteaga, Ryan O'Hara, Alice Mazzagatti, Emily Ballard, Yingying Hu, Alex Pan, Daniel A Schmitz, Yulei Wei, Masahiro Sakurai, Peter Ly, Laura A Banaszynski, Jun Wu

{"title":"TASOR expression in naive embryonic stem cells safeguards their developmental potential.","authors":"Carlos A Pinzon-Arteaga, Ryan O'Hara, Alice Mazzagatti, Emily Ballard, Yingying Hu, Alex Pan, Daniel A Schmitz, Yulei Wei, Masahiro Sakurai, Peter Ly, Laura A Banaszynski, Jun Wu","doi":"10.1016/j.celrep.2024.114887","DOIUrl":null,"url":null,"abstract":"<p><p>The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs. Notably, the survival of Tasor knockout PSCs during this transition can be restored by inhibiting caspase or deleting the mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to cell death specifically in cells exiting naive pluripotency. Our findings highlight the importance of epigenetic programs established in naive pluripotency for normal development.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":"43 11","pages":"114887"},"PeriodicalIF":7.5000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell reports","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.celrep.2024.114887","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The seamless transition through stages of pluripotency relies on a balance between transcription factor networks and epigenetic mechanisms. Here, we reveal the crucial role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in maintaining cell viability during the transition from naive to primed pluripotency. TASOR loss in naive pluripotent stem cells (PSCs) triggers replication stress, disrupts H3K9me3 heterochromatin, and impairs silencing of LINE-1 (L1) transposable elements, with more severe effects in primed PSCs. Notably, the survival of Tasor knockout PSCs during this transition can be restored by inhibiting caspase or deleting the mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to cell death specifically in cells exiting naive pluripotency. Our findings highlight the importance of epigenetic programs established in naive pluripotency for normal development.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

TASOR 在幼稚胚胎干细胞中的表达可保护其发育潜能。

多能性各阶段的无缝过渡依赖于转录因子网络和表观遗传机制之间的平衡。在这里，我们揭示了转基因激活抑制因子（TASOR）在维持细胞从幼稚多能性过渡到原始多能性过程中的活力方面的关键作用，TASOR是人类沉默中枢（HUSH）复合体的一个组成部分。在幼稚多能干细胞（PSCs）中，TASOR的缺失会引发复制应激，破坏H3K9me3异染色质，并损害LINE-1（L1）转座元件的沉默，对原始多能干细胞的影响更为严重。值得注意的是，通过抑制 Caspase 或删除线粒体抗病毒信号蛋白（MAVS），Tasor 基因敲除的 PSCs 在这一转变过程中的存活率可以恢复。这表明，计划外的L1表达激活了先天性免疫反应，导致细胞死亡，特别是在脱离幼稚多能性的细胞中。我们的发现凸显了在幼稚多能性中建立的表观遗传程序对正常发育的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.