김진용 (서울대학교 의과대학, Columbia University) | 한빛사논문 > 한빛사

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서울대학교 의과대학, Columbia University

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Cell Reports, Volume 39, Issue 7, 17 May 2022, 110821 | https://doi.org/10.1016/j.celrep.2022.110821 Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts

Jin Yong Kim,^1,2,3,4,8 Minji Park,^1,2,3,5,8 Jungyoon Ohn,^1,2,3 Rho Hyun Seong,⁶ Jin Ho Chung,^1,2,3,5 Kyu Han Kim,^1,2,3 Seong Jin Jo,^1,2,3,* and Ohsang Kwon^{1,2,3,5,7,9,*}

¹Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea
²Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea
³Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea
⁴Department of Dermatology, Columbia University, New York 10032, NY, USA
⁵Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
⁶Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea
⁷Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, Korea
⁸These authors contributed equally.
⁹Lead contact

^*Correspondence

Abstract

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.

논문정보

형식Research article
게재일2022년 05월 (BRIC 등록일 2022-07-25)
연구진국내(교신)+국외 연구진
분야 의약학 > 응용의학

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