Journal of dermatological science · 2024
Dermal fibroblasts retain site-specific transcriptomic identity in keloids.
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Lin Pingping, Zhang Daoning, Tian Jie, Lai Binbin, Yang Yu, Yan Yicen, Zhang Shenxi, Zhang Guohong, Li Hang
Аннотация
BACKGROUND: Human skin displays extensive spatial heterogeneity and maintains distinct positional identity. However, the impact of disease processes on these site-specific differences remains poorly understood, especially in keloid, a skin disorder characterized by pronounced spatial heterogeneity.
OBJECTIVE: This study aimed to assess whether the spatial heterogeneity and positional identity observed in different anatomic sites persist in keloids.
METHODS: Transcriptome sequencing was conducted on 139 keloid dermal tissues and 19 keloid fibroblast samples spanning seven distinct anatomic sites to identify the spatial transcriptomic heterogeneity. In addition, single-cell RNA sequencing data were utilized to elucidate the contributions of various cell types to the maintenance of positional identity.
RESULTS: Keloid dermal tissues from diverse sites were categorized into three anatomic groupings: trunk and extremity, ear, and mandible regions. Enrichment analysis of differentially expressed genes unveiled that keloids across distinct regions retained unique anatomically-related gene expression profiles, reminiscent of those observed in normal skin. Notably, regional disparities consistently prevailed and surpassed inter-donor variations. Single-cell RNA sequencing further revealed that mesenchymal cells, particularly fibroblasts, made major contributions to positional identity in keloids. Moreover, gene expression profiles in primary keloid fibroblasts demonstrated a remarkable persistence of positional identity, enduring even after prolonged in vitro propagation.
CONCLUSION: Taken together, these findings imply that keloids remain positional identity and developmental imprinting characteristic of normal skin. Fibroblasts predominantly contribute to the spatial heterogeneity observed in keloids.
OBJECTIVE: This study aimed to assess whether the spatial heterogeneity and positional identity observed in different anatomic sites persist in keloids.
METHODS: Transcriptome sequencing was conducted on 139 keloid dermal tissues and 19 keloid fibroblast samples spanning seven distinct anatomic sites to identify the spatial transcriptomic heterogeneity. In addition, single-cell RNA sequencing data were utilized to elucidate the contributions of various cell types to the maintenance of positional identity.
RESULTS: Keloid dermal tissues from diverse sites were categorized into three anatomic groupings: trunk and extremity, ear, and mandible regions. Enrichment analysis of differentially expressed genes unveiled that keloids across distinct regions retained unique anatomically-related gene expression profiles, reminiscent of those observed in normal skin. Notably, regional disparities consistently prevailed and surpassed inter-donor variations. Single-cell RNA sequencing further revealed that mesenchymal cells, particularly fibroblasts, made major contributions to positional identity in keloids. Moreover, gene expression profiles in primary keloid fibroblasts demonstrated a remarkable persistence of positional identity, enduring even after prolonged in vitro propagation.
CONCLUSION: Taken together, these findings imply that keloids remain positional identity and developmental imprinting characteristic of normal skin. Fibroblasts predominantly contribute to the spatial heterogeneity observed in keloids.