Stem cell activity-coupled suppression of endogenous retrovirus governs adult tissue regeneration.

Autor:	Lyu Y; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kim SJ; Department of Epigenetics and Molecular Carcinogenesis, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA., Humphrey ES; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA., Nayak R; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA., Guan Y; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Liang Q; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Kim KH; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Tan Y; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Dou J; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Sun H; Department of Genome Medicine, UT MD Anderson Cancer Center, Houston, TX, USA., Song X; Department of Genome Medicine, UT MD Anderson Cancer Center, Houston, TX, USA., Nagarajan P; Department of Anatomical Pathology, UT MD Anderson Cancer Center, Houston, TX, USA., Gerner-Mauro KN; Department of Pulmonary Medicine, UT MD Anderson Cancer Center, Houston, TX, USA; Development, Disease Models, and Therapeutics Graduate Program, Baylor College of Medicine, Houston, TX, USA., Jin K; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Wiess School of Natural Sciences, Rice University, Houston, TX, USA., Liu V; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Wiess School of Natural Sciences, Rice University, Houston, TX, USA., Hassan RH; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Johnson ML; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Deliu LP; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., You Y; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sharma A; Electron Microscopy Resource Center, The Rockefeller University, New York, NY, USA., Pasolli HA; Electron Microscopy Resource Center, The Rockefeller University, New York, NY, USA., Lu Y; Department of Epigenetics and Molecular Carcinogenesis, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA., Zhang J; Department of Genome Medicine, UT MD Anderson Cancer Center, Houston, TX, USA., Mohanty V; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Chen K; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX, USA., Yang YJ; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chen T; Department of Epigenetics and Molecular Carcinogenesis, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA., Ge Y; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Graduate School of Biomedical Sciences, UT MD Anderson Cancer Center UTHealth Houston, Houston, TX, USA. Electronic address: yge1@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Oct 23. Date of Electronic Publication: 2024 Oct 23.
DOI:	10.1016/j.cell.2024.10.007
Abstrakt:	Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in murine skin. SETDB1 ablation leads to the reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and the assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair follicle stem cells and progenitors and antiviral-independent response due to replication stress in transient amplifying cells. ERV reactivation is promoted by DNA demethylase ten-eleven translocation (TET)-mediated hydroxymethylation and recapitulated by ablating cell fate transcription factors. Together, we demonstrated ERV silencing is coupled with stem cell activity and essential for adult hair regeneration. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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