CMTM3 overexpression promotes cell apoptosis while DHT promotes cell proliferation in hair follicle stem cells (HFSCs).

In Yangtze River Delta white goat, hypermethylation of CMTM3 leads to a decreased expression level in high quality brush hair. However, the regulation of CMTM3 expression and its function in hair follicle stem cells (HFSCs) remains largely unknown. In this study, we investigated the regulation of CMTM3 expression, function, and molecular mechanism in HFSCs. The re-expression of CMTM3 significantly suppressed the proliferation of HFSCs by inducing G1 cell cycle arrest and promoting apoptosis. Moreover, the downregulation of CMTM3 promoted HFSC proliferation. Treatment with sh_CMTM3 and incubation in a DHT culture medium had the most significant growth-promoting effect. It was hypothesized that transcriptome analysis using RNA sequencing (RNA-seq) in samples would enable the identification of unique protein-coding and non-coding genes that may help uncover the role of CMTM3. Multiple genes and pathways were involved in this process, including 168 common DEGs, such as CXCL8 and E-selectin, which is reportedly involved in multiple regulatory pathways. These results indicated that CMTM3 can function as HFSCs through the induction of a G1 cell cycle arrest and promoted apoptosis by mediating crosstalk between several pathways and transcription factors. Our data is available in the National Center for Biotechnology Information (NCBI) database with the accession number PRJNA657430. • A high expression level of CMTM3 inhibited the proliferation of hair follicle stem cells (HFSCs) and promoted cell apoptosis. Conversely, inhibiting the expression level of CMTM3 and adding androgens promoted the proliferation of HFSCs. • RNA-seq analysis showed that the differentially expressed genes (DEGs) related to CMTM3 were mainly connected to vasculature, the cardiovascular system, and the immune system. [ABSTRACT FROM AUTHOR]