Biology subjects

Acosta-Herrera, M.

Publications and source records attributed to Acosta-Herrera, M..

2 recordsLinked to original sources

bioRxiv2026

Sex-biased Fibroblast Subpopulations and Transcriptional Programs Reveal Mechanisms of Skin Lesion Development in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with pronounced sex differences: females are more frequently affected and males develop more severe skin fibrosis. The cellular mechanisms of this disparity remain unclear. Here we use single-cell transcriptomics of lesional, non-lesional, and healthy skin to define fibroblast states and sex-biased transcriptional programs during lesion development. We identify a sex-dependent divergence in SSc fibrotic regulation. Female fibroblasts exhibit heightened inflammatory signaling and canonical TGF-{beta}-driven extracellular matrix production, whereas male fibroblasts preferentially engage non-canonical TGF-{beta} pathways, mechanotransduction, and MYC-associated stress programs. We further reveal that the fibrotic lesional environment shows sex differences: SFRP2DPP4 fibroblasts predominate in females and COL11A1/COCH in males. Our findings uncover cellular mechanisms underlying sex differences in SSc fibrosis, highlight opportunities for sex-informed therapeutic strategies and underscore the necessity of integrating biological sex into precision medicine frameworks to identify divergent molecular drivers of fibrotic disease.

genomics↗

bioRxiv2026

Single-Cell RNA Sequencing Reveals Impaired Regulatory T Cell Function and a Pro-inflammatory Th17 Profile in Systemic Sclerosis

ObjectiveThis resource deeply characterizes the CD4+ T cell subpopulations populations in SSc patients, with a novel single-cell RNA sequencing (scRNA-seq) approach, offering unprecedented insights into the cellular and molecular underpinnings of the disease. MethodsWe performed scRNA-seq to analyze over 80,000 CD4+ T cells from 8 SSc patients and 8 healthy controls, integrating abundance, transcriptional, and TCR repertoire analysis, to define CD4+ T cell subtype-specific signatures associated with SSc. ResultsSSc CD4+ T cells displayed a global interferon-driven activation signature and significantly reduced TNF signaling. Key transcriptomic alterations included the downregulation of SOX4 and CD83, alongside an expansion of Th2 and proinflammatory, steroid-resistant Th17 cells. Furthermore, Tregs exhibited a destabilized state characterized by high FCRL3 and reduced FOXP3 expression. Finally, TCR repertoire analysis identified increased clonal expansion specifically within the central memory (Tcm) compartment. ConclusionTogether, this data revealed SSc-associated cell population states in CD4+ T cells with unique transcriptomic signatures and provided a publicly accessible interactive platform to facilitate exploration of this dataset by the research community.

genetics↗