Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development

The transition between the mesenchyme and epithelium contributes to the development of various tissues. During skin development, epithelial-mesenchymal transition in the ectodermal epithelia is involved in the development of the dermal mesenchyme in early embryos. However, the precise roles and func...

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Main Authors: Yoshikazu Hirose, Asaka Miura, Yuya Ouchi, Tomomi Kitayama, Souki Omura, Takashi Shimbo, Akio Tanaka, Manabu Fujimoto, Kotaro Saga, Katsuto Tamai
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580825000937
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author Yoshikazu Hirose
Asaka Miura
Yuya Ouchi
Tomomi Kitayama
Souki Omura
Takashi Shimbo
Akio Tanaka
Manabu Fujimoto
Kotaro Saga
Katsuto Tamai
author_facet Yoshikazu Hirose
Asaka Miura
Yuya Ouchi
Tomomi Kitayama
Souki Omura
Takashi Shimbo
Akio Tanaka
Manabu Fujimoto
Kotaro Saga
Katsuto Tamai
author_sort Yoshikazu Hirose
collection DOAJ
description The transition between the mesenchyme and epithelium contributes to the development of various tissues. During skin development, epithelial-mesenchymal transition in the ectodermal epithelia is involved in the development of the dermal mesenchyme in early embryos. However, the precise roles and functions of epithelial-mesenchymal/mesenchymal-epithelial transition in cutaneous development have not been fully elucidated. In this study, we aimed to elucidate these roles and functions in the neonatal mouse skin. We conducted single-cell RNA sequencing and immunohistochemical analyses to search for Pdgfra-expressing (Pα+) fibroblasts with transition activities to/from Krt5-expressing keratinocytes. We determined that the Pα+/Krt5-lineage (K5lin+) fibroblasts significantly contributed to developing hair follicle dermal stem cells to generate lower dermal papilla cells and lower dermal sheath cells. In the developing mouse skin, K5lin+ fibroblasts appeared concurrently with hair follicle development and formed outer edge cells in the early dermal papilla on embryonic day 16.5. K5lin+ hair follicle mesenchymal cells were also maintained in aged mouse skin. These results provide insights into the role and function of the transition between the mesenchyme and epithelium in hair follicle development and maintenance.
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spelling doaj-art-aafb23a4cc67490eb6acf0759e50010f2025-08-20T02:37:38ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210200610.1016/j.bbrep.2025.102006Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme developmentYoshikazu Hirose0Asaka Miura1Yuya Ouchi2Tomomi Kitayama3Souki Omura4Takashi Shimbo5Akio Tanaka6Manabu Fujimoto7Kotaro Saga8Katsuto Tamai9Department of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, JapanSchool of Medicine, Hiroshima University, Hiroshima, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Suita, Osaka, JapanDepartment of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, JapanDepartment of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, JapanDepartment of Stem Cell Therapy Science, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; StemRIM Inc., Ibaraki, Osaka, Japan; Corresponding author. Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.The transition between the mesenchyme and epithelium contributes to the development of various tissues. During skin development, epithelial-mesenchymal transition in the ectodermal epithelia is involved in the development of the dermal mesenchyme in early embryos. However, the precise roles and functions of epithelial-mesenchymal/mesenchymal-epithelial transition in cutaneous development have not been fully elucidated. In this study, we aimed to elucidate these roles and functions in the neonatal mouse skin. We conducted single-cell RNA sequencing and immunohistochemical analyses to search for Pdgfra-expressing (Pα+) fibroblasts with transition activities to/from Krt5-expressing keratinocytes. We determined that the Pα+/Krt5-lineage (K5lin+) fibroblasts significantly contributed to developing hair follicle dermal stem cells to generate lower dermal papilla cells and lower dermal sheath cells. In the developing mouse skin, K5lin+ fibroblasts appeared concurrently with hair follicle development and formed outer edge cells in the early dermal papilla on embryonic day 16.5. K5lin+ hair follicle mesenchymal cells were also maintained in aged mouse skin. These results provide insights into the role and function of the transition between the mesenchyme and epithelium in hair follicle development and maintenance.http://www.sciencedirect.com/science/article/pii/S2405580825000937EMT/METSkin developmentHair follicle dermal stem cellSingle-cell RNA sequencing
spellingShingle Yoshikazu Hirose
Asaka Miura
Yuya Ouchi
Tomomi Kitayama
Souki Omura
Takashi Shimbo
Akio Tanaka
Manabu Fujimoto
Kotaro Saga
Katsuto Tamai
Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
Biochemistry and Biophysics Reports
EMT/MET
Skin development
Hair follicle dermal stem cell
Single-cell RNA sequencing
title Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
title_full Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
title_fullStr Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
title_full_unstemmed Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
title_short Fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
title_sort fibroblasts fluctuating between mesenchyme and epithelium are involved in hair follicle mesenchyme development
topic EMT/MET
Skin development
Hair follicle dermal stem cell
Single-cell RNA sequencing
url http://www.sciencedirect.com/science/article/pii/S2405580825000937
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