Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
Dermal fibroblasts lose stem cell potency after birth, which prevents regenerative healing. However, the underlying intracellular mechanisms are largely unknown. We uncover the postnatal maturation of papillary fibroblasts (PFs) driven by the extensive Twist2-mediated remodeling of chromatin accessibility. A loss of the regenerative ability of postnatal PFs occurs with decreased H3K27ac levels. Single-cell transcriptomics, assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) reveal the postnatal maturation trajectory associated with the loss of the regenerative trajectory in PFs, which is characterized by a marked decrease in chromatin accessibility and H3K27ac modifications. Histone deacetylase inhibition delays spontaneous chromatin remodeling, thus maintaining the regenerative ability of postnatal PFs. Genomic analysis identifies Twist2 as a major regulator within chromatin regions with decreased accessibility during the postnatal period. When Twist2 is genetically deleted in dermal fibroblasts, the intracellular cascade of postnatal maturation is significantly delayed. Our findings reveal the comprehensive intracellular mechanisms underlying intrinsic postnatal changes in dermal fibroblasts.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Cell reports - 39(2022), 7 vom: 17. Mai, Seite 110821 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Jin Yong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.05.2022 Date Revised 15.08.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2022.110821 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341074322 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Dermal fibroblasts lose stem cell potency after birth, which prevents regenerative healing. However, the underlying intracellular mechanisms are largely unknown. We uncover the postnatal maturation of papillary fibroblasts (PFs) driven by the extensive Twist2-mediated remodeling of chromatin accessibility. A loss of the regenerative ability of postnatal PFs occurs with decreased H3K27ac levels. Single-cell transcriptomics, assay for transposase-accessible chromatin sequencing (ATAC-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) reveal the postnatal maturation trajectory associated with the loss of the regenerative trajectory in PFs, which is characterized by a marked decrease in chromatin accessibility and H3K27ac modifications. Histone deacetylase inhibition delays spontaneous chromatin remodeling, thus maintaining the regenerative ability of postnatal PFs. Genomic analysis identifies Twist2 as a major regulator within chromatin regions with decreased accessibility during the postnatal period. When Twist2 is genetically deleted in dermal fibroblasts, the intracellular cascade of postnatal maturation is significantly delayed. Our findings reveal the comprehensive intracellular mechanisms underlying intrinsic postnatal changes in dermal fibroblasts | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Developmental biology | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a H3K27ac modifications | |
| 650 | 4 | |a Twist2 | |
| 650 | 4 | |a chromatin accessibility | |
| 650 | 4 | |a dermal fibroblast | |
| 650 | 4 | |a hair follicle | |
| 650 | 4 | |a papillary fibroblast | |
| 650 | 4 | |a postnatal maturation | |
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| 650 | 7 | |a Transposases |2 NLM | |
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| 700 | 1 | |a Park, Minji |e verfasserin |4 aut | |
| 700 | 1 | |a Ohn, Jungyoon |e verfasserin |4 aut | |
| 700 | 1 | |a Seong, Rho Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Jin Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kyu Han |e verfasserin |4 aut | |
| 700 | 1 | |a Jo, Seong Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Kwon, Ohsang |e verfasserin |4 aut | |
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