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

Autor:	Pinzon-Arteaga CA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., O'Hara R; Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics and Gynecology, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Mazzagatti A; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Ballard E; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hu Y; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Pan A; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; St. Mark's School of Texas, Dallas, TX 75230, USA., Schmitz DA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Wei Y; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China., Sakurai M; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Ly P; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Cell Biology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Banaszynski LA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics and Gynecology, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: laura.banaszynski@utsouthwestern.edu., Wu J; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics and Gynecology, Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jun2.wu@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Nov 26; Vol. 43 (11), pp. 114887. Date of Electronic Publication: 2024 Oct 24.
DOI:	10.1016/j.celrep.2024.114887
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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