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Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration

Given that adult stem cells (ASCs) fuel homeostasis and healing by providing tissue-specific descendants, the fidelity of ASC fate determination is crucial for regeneration. Here, we established that an epigenetic control of epithelial ASC fate fidelity via Ezh2/H3K27me3 was indispensable for inciso...

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Autores principales: Yu, Fanyuan, Li, Feifei, Zheng, Liwei, Ye, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307244/
https://www.ncbi.nlm.nih.gov/pubmed/35867784
http://dx.doi.org/10.1126/sciadv.abn4977
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author Yu, Fanyuan
Li, Feifei
Zheng, Liwei
Ye, Ling
author_facet Yu, Fanyuan
Li, Feifei
Zheng, Liwei
Ye, Ling
author_sort Yu, Fanyuan
collection PubMed
description Given that adult stem cells (ASCs) fuel homeostasis and healing by providing tissue-specific descendants, the fidelity of ASC fate determination is crucial for regeneration. Here, we established that an epigenetic control of epithelial ASC fate fidelity via Ezh2/H3K27me3 was indispensable for incisor homeostasis and regeneration. Mechanistically, in homeostasis, H3K27me3 upstream occupies the Sonic hedgehog (Shh) promoter to directly restrain Shh expression, thereby precisely confining Shh expression. When injury occurred, Ezh2/H3K27me3 was substantially induced within inner enamel epithelium and preameloblast zones, and such epigenetic response guaranteed the fidelity of ASC commitment via pulling injury-increased Shh back to homeostatic levels, utterly underlying regeneration progression. Once losing H3K27me3-dependent restriction of Shh expression through the Cre-Loxp system totally disrupted lineage commitment and stemness exhaustion, and abolished hard tissue regeneration emerged in vivo. We next uncovered the molecular mechanisms by which injury-induced Ezh2 mediated the spatiotemporal dynamics of H3K27me3 to repress Shh expression, thus epigenetically deciding ASC fate.
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spelling pubmed-93072442022-08-09 Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration Yu, Fanyuan Li, Feifei Zheng, Liwei Ye, Ling Sci Adv Biomedicine and Life Sciences Given that adult stem cells (ASCs) fuel homeostasis and healing by providing tissue-specific descendants, the fidelity of ASC fate determination is crucial for regeneration. Here, we established that an epigenetic control of epithelial ASC fate fidelity via Ezh2/H3K27me3 was indispensable for incisor homeostasis and regeneration. Mechanistically, in homeostasis, H3K27me3 upstream occupies the Sonic hedgehog (Shh) promoter to directly restrain Shh expression, thereby precisely confining Shh expression. When injury occurred, Ezh2/H3K27me3 was substantially induced within inner enamel epithelium and preameloblast zones, and such epigenetic response guaranteed the fidelity of ASC commitment via pulling injury-increased Shh back to homeostatic levels, utterly underlying regeneration progression. Once losing H3K27me3-dependent restriction of Shh expression through the Cre-Loxp system totally disrupted lineage commitment and stemness exhaustion, and abolished hard tissue regeneration emerged in vivo. We next uncovered the molecular mechanisms by which injury-induced Ezh2 mediated the spatiotemporal dynamics of H3K27me3 to repress Shh expression, thus epigenetically deciding ASC fate. American Association for the Advancement of Science 2022-07-22 /pmc/articles/PMC9307244/ /pubmed/35867784 http://dx.doi.org/10.1126/sciadv.abn4977 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Yu, Fanyuan
Li, Feifei
Zheng, Liwei
Ye, Ling
Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title_full Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title_fullStr Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title_full_unstemmed Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title_short Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
title_sort epigenetic controls of sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307244/
https://www.ncbi.nlm.nih.gov/pubmed/35867784
http://dx.doi.org/10.1126/sciadv.abn4977
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