Single-Cell transcriptomics unveils metabolic and cellular dysregulation in striae gravidarum
Yu Cheng1, Chen Liang1, Zixin Cai2
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Striae gravidarum (SG) is a common skin condition characterized by disrupted dermal extracellular matrix (ECM) homeostasis. Despite its high prevalence, the underlying cellular and molecular pathogenesis remains poorly understood, particularly regarding fibroblast heterogeneity and metabolic dysregulation.
Objectives:
This study aimed to delineate the cellular landscape and molecular mechanisms of SG at single-cell resolution, with a focus on fibroblast subpopulation dynamics, intercellular communication, and metabolic reprogramming.
Methods:
We performed integrated single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) on dermal specimens from human SG lesions and matched normal skin. Functional validation was conducted using qPCR, histological staining (H&E, EVG, picrosirius red), immunofluorescence, and Mendelian randomization analysis.
Results:
SG skin exhibited significant cellular reorganization, with fibroblasts showing the most profound transcriptional changes. Intercellular communication analysis identified a dysregulated sender-receiver axis between the inflammatory, metabolically active sC7 subset and the reparative sC5 subset. Pseudotime analysis indicated a blocked differentiation from sC7 to sC5. The sC7 subset underwent specific fatty acid metabolic reprogramming, marked by upregulation of key enzymes including ACSBG1. Triacsin C treatment in primary PDPN⁺ reticular fibroblasts suppressed ECM gene expression and attenuated pro-fibrotic markers; notably, it also downregulated representative sC7-associated genes while upregulating sC5-associated genes, suggesting partial restoration of a reparative transcriptional program. Furthermore, local Acsbg1 silencing in dorsal skin alleviated SG-like dermal remodeling in the mouse model, with improved dermal architecture, collagen organization, and elastic fiber integrity.
Conclusions:
Targeting ACSBG1-mediated fatty acid metabolic reprogramming in pro-fibrotic fibroblast subsets restores a reparative transcriptional programme and ameliorates dermal ECM disruption in SG. These findings identify ACSBG1 as a potential therapeutic target for SG.
