TASOR expression in naive embryonic stem cells safeguards their developmental potential

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.

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Publication Details

Journal
Cell Reports
Published
2024-10-24
DOI
https://doi.org/10.1016/j.celrep.2024.114887
Citations
2
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
0.47

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article

TASOR expression in naive embryonic stem cells safeguards their developmental potential

Emily Ballard, Alice Mazzagatti, Peter Ly, Ryan O’Hara et al.
2 citations
Cell Reports
CRISPR and Genetic Engineering
0.47
article

TASOR expression in naive embryonic stem cells safeguards their developmental potential

Emily Ballard, Alice Mazzagatti, Peter Ly, Ryan O’Hara, Masahiro Sakurai, Daniel A. Schmitz, Jun Wu, Yulei Wei, Alex Pan, Laura A. Banaszynski, Carlos A. Pinzón-Arteaga, Yingying Hu
article en
2 citations

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.

Cell ReportsVol. 43(11)
Southwestern Medical Center (US), The University of Texas Southwestern Medical Center (US)
American Cancer Society, Welch Foundation, Cancer Prevention and Research Institute of Texas, University of Texas Southwestern Medical Center, National Institutes of Health
Gender equality
Openalex Percentile: Top 34%
CRISPR and Genetic Engineering
0.47
DOIOpen Access PDFOpenAlex
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