ISID1342 - Spatial transcriptome profiling reveals TGFβ-2 in hair follicle progenitor cells is a potential driver of androgenetic alopecia

Progenitor (PG) cells of the hair follicle are vital to hair growth and regeneration. Previous reports have highlighted their substantial reduction in the hair follicle from androgenetic alopecia (AGA) scalps. Since there is a limitation in either investigating human hair follicle PG in their native context or isolation for in vitro studies, no study focuses on molecular mechanisms underlying PG cell loss in the pathogenesis of AGA . Here, the state-of-the-art spatial whole transcriptome analysis of the PG regions revealed the potential mechanism driving PG loss in AGA using the human intact scalp samples. NanoString GeoMxTM Whole Transcriptome Atlas (WTA) was used to perform spatial transcriptome analysis. The gene expression profiles of PG regions of the hair follicle from early AGA (PG-A) and control (PG-C) scalp tissues were compared to identify and analyze the major molecular alterations, including biological processes and candidate potential upstream regulators. Immunohistochemistry (IHC) with digital image analysis was used to validate the results. A comparison of gene expression between PG-A and PG-C regions revealed 197 differentially expressed genes. Pathway enrichment analysis identified transforming growth factor beta (TGF-β) production as one of the significantly disturbed biological processes. QIAGEN Ingenuity Pathway Analysis (IPA) showed that TGFB2, an upregulated gene in PG-A, was a potential upstream regulator driving the transcriptional alterations. Reassuringly, we detected significantly increased TGFβ-2 immunostaining in PG-A. Conclusively, spatial profiling revealed molecular perturbation of hair follicle PG from early AGA scalps with an intact microenvironment. We identified that TGFβ-2 might be a potential player in driving PG loss in AGA.