ヒト毛周期に伴う皮膚組織再構築の仕組み~1細胞解析により毛周期の時間軸を再構成~

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2025-09-05 理化学研究所,ポーラ化成工業株式会社

理化学研究所とポーラ化成工業の共同研究チームは、ヒト毛周期に伴う皮膚組織再構築の分子機構を1細胞遺伝子発現解析で解明した。毛包を1つ含む19個のヒト皮膚片からデータを取得し、遺伝子発現パターンの類似性に基づき毛周期の「疑似時間軸」を再構築。その結果、休止期・成長期・退行期に応じて16種類の細胞種が協調的に遺伝子発現を変化させることを確認した。特に退行期では、毛包角化細胞のアポトーシスに伴い、周囲の線維芽細胞・血管内皮細胞・白血球が活性化し、細胞外マトリックス(ECM)の分解と新生が進行することで皮膚組織が再構築される仕組みを明らかにした。本成果は、ヒト組織再生の基本原理解明に加え、脱毛症など毛周期関連疾患の新規治療法開発への応用が期待される。

ヒト毛周期に伴う皮膚組織再構築の仕組み~1細胞解析により毛周期の時間軸を再構成~
ヒト毛周期の時系列的な解析から見いだした皮膚組織再構築の仕組み

<関連情報>

ヒト毛周期の単一細胞トランスクリプトーム再構築:皮膚組織リモデリングの時間的動態の捕捉 Single-cell transcriptomic reconstruction of the human hair cycle: Capturing the temporal dynamics of skin tissue remodeling

Jun Yokota ∙ Takamasa Gomi ∙ Yasuko Harada ∙ … ∙ Hiroki Machida ∙ Yuki Shirai ∙ Hironobu Fujiwara
Cell Reports  Published:August 28, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.116196

Highlights

  • A single-cell dataset reveals hair-cycle-dependent shifts in cellular states and interactions
  • Fibroblasts, vessels, and leukocytes contribute to tissue remodeling in regressing follicles
  • ECM remodeling, angiogenesis, and phagocytosis proceed sequentially during regression
  • Three cell populations signal reciprocally with follicular keratinocytes during regression

Summary

The hair cycle is a valuable model for studying tissue remodeling processes in adult mammals. Time course single-cell transcriptomics offers a powerful approach for characterizing changes in cellular states and interactions; however, its application in human tissues remains challenging. Here, we performed single-cell RNA sequencing on 19 human skin tissues, each containing a single hair follicle. We reconstructed a pseudotemporal progression of the hair cycle—termed the “pseudo-hair cycle”—by computationally ordering samples according to their gene expression profiles. The pseudo-hair cycle delineates the continuum of gene expression changes occurring in 16 distinct epithelial and dermal cell populations throughout the hair cycle, revealing specific cellular states and interactions. We identified hair follicle keratinocytes, dermal sheath fibroblasts, vascular endothelial cells, and leukocytes as key contributors to tissue remodeling during catagen. Our study provides a high-resolution temporal dataset for investigating the dynamic molecular and cellular mechanisms underlying skin remodeling in humans.

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