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Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
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Dermal fibroblasts retain site-specific transcriptomic identity in keloids.

Pingping Lin1, Daoning Zhang1, Jie Tian2

  • 1Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China; National Clinical Research Center for Skin and Immune Diseases, Beijing, China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China; NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China.

Journal of Dermatological Science
|September 25, 2024
PubMed
Summary

Keloids retain skin's positional identity and spatial differences across body sites. Fibroblasts are key to this heterogeneity, even in lab conditions, showing developmental imprinting.

Keywords:
keloidpositional identityspatial heterogeneitytranscriptome sequencing

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Area of Science:

  • Dermatology
  • Genomics
  • Cell Biology

Background:

  • Human skin exhibits significant spatial heterogeneity and positional identity.
  • The influence of disease on these site-specific differences is unclear, particularly in keloids.

Purpose of the Study:

  • To determine if spatial heterogeneity and positional identity persist in keloids.
  • To investigate the role of cell types in maintaining keloid positional identity.

Main Methods:

  • Transcriptome sequencing of 139 keloid tissues and 19 fibroblast samples from seven anatomic sites.
  • Single-cell RNA sequencing to analyze cell type contributions to positional identity.

Main Results:

  • Keloids maintained distinct, anatomically-related gene expression profiles across different body regions.
  • Regional differences in keloids exceeded variations between donors.
  • Mesenchymal cells, especially fibroblasts, were crucial for keloid positional identity.
  • Fibroblast positional identity persisted even after extended in vitro culture.

Conclusions:

  • Keloids exhibit positional identity and developmental imprinting similar to normal skin.
  • Fibroblasts are the primary drivers of spatial heterogeneity in keloids.