Twist2-driven chromatin remodeling governs the postnatal maturation of dermal fibroblasts
Jin Yong Kim,
Minji Park,
Jungyoon Ohn,
Rho Hyun Seong,
Jin Ho Chung,
Kyu Han Kim,
Seong Jin Jo,
Ohsang Kwon
Affiliations
Jin Yong Kim
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea; Department of Dermatology, Columbia University, New York 10032, NY, USA
Minji Park
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
Jungyoon Ohn
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea
Rho Hyun Seong
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Korea
Jin Ho Chung
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
Kyu Han Kim
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea
Seong Jin Jo
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea; Corresponding author
Ohsang Kwon
Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, Korea; Corresponding author
Summary: 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.
