Insights into the regulation of MAP3K1 in hair follicle stem cells by transcriptome analysis

MAP3K1 is a significant member of the MAPK family, and its expressed MEKK1 protein has a wide range of biological activities and is an essential node in the MAPK signaling pathway. A significant number of studies have revealed that MAP3K1 plays a complicated function in the control of cell proliferation, apoptosis, invasion and movement, participates in the regulation of the immune system, and plays an important role in wound healing, tumorigenesis and other processes. In this study, we looked at the involvement of MAP3K1 in the control of hair follicle stem cells (HFSCs). Overexpression of MAP3K1 significantly promoted the proliferation of HFSCs by inhibiting apoptosis and promoting the transition from S phase to G2 phase. The transcriptome identified 189 (MAP3K1_OE) and 414 (MAP3K1_sh) differential genes. The two pathways with the most significant enrichment of differentially expressed genes were the IL-17 signaling pathway and TNF signaling pathway, and the significantly enriched terms in the GO enrichment analysis involved regulation of response of external stimulus, inflammatory and cytokine. Indicate that MAP3K1 can function as a promoting factor in HFSCs through the induction of cell cycle transition from S phase to G2 phase can inhibition apoptosis by mediating crosstalk among several pathways and cytokines.HIGHLIGHTSAbnormal MAP3K1 expression in hair follicle stem cells (HFSCs) can impair HFSC proliferation and apoptosis.MAP3K1 controls hair follicle stem cell proliferation via modulating cell apoptosis and the ratio of cells in S phase/G2 phase.The differential genes shared by MAP3K1_sh and MAP3K1_OE are enriched in GO terms such as inflammation, adipocyte differentiation, acute inflammation, and so on. Abnormal MAP3K1 expression in hair follicle stem cells (HFSCs) can impair HFSC proliferation and apoptosis. MAP3K1 controls hair follicle stem cell proliferation via modulating cell apoptosis and the ratio of cells in S phase/G2 phase. The differential genes shared by MAP3K1_sh and MAP3K1_OE are enriched in GO terms such as inflammation, adipocyte differentiation, acute inflammation, and so on.

MAP3K1是丝裂原活化蛋白激酶（Mitogen-Activated Protein Kinase, MAPK）家族的重要成员，其表达产生的MEKK1蛋白具有广泛的生物学活性，是MAPK信号通路中的关键调控节点。诸多研究证实，MAP3K1在细胞增殖、凋亡、侵袭与迁移的调控中发挥复杂功能，参与免疫系统的调控，并在伤口愈合、肿瘤发生等过程中发挥关键作用。本研究聚焦探讨了MAP3K1对毛囊干细胞（hair follicle stem cells, HFSCs）的调控作用。过表达MAP3K1可通过抑制细胞凋亡、促进细胞周期从S期向G2期转换，显著促进毛囊干细胞的增殖。通过转录组测序筛选得到189个MAP3K1过表达组（MAP3K1_OE）差异基因与414个MAP3K1敲低组（MAP3K1_sh）差异基因。差异表达基因富集最为显著的两条通路为IL-17信号通路与TNF信号通路；基因本体（Gene Ontology, GO）富集分析中显著富集的功能条目涵盖外界刺激应答调控、炎症反应与细胞因子应答等。研究结果表明，MAP3K1可通过介导多条通路与细胞因子间的串扰，诱导细胞周期从S期向G2期转换并抑制细胞凋亡，从而在毛囊干细胞中充当促增殖因子。

研究亮点
毛囊干细胞中MAP3K1表达异常可损害其增殖能力并干扰细胞凋亡进程；MAP3K1通过调控细胞凋亡与S期/G2期细胞比例，控制毛囊干细胞的增殖活性；MAP3K1敲低组（MAP3K1_sh）与过表达组（MAP3K1_OE）的共有差异基因富集于炎症、脂肪细胞分化、急性炎症等GO功能条目。
毛囊干细胞中MAP3K1表达异常可损害其增殖能力并干扰细胞凋亡进程；MAP3K1通过调控细胞凋亡与S期/G2期细胞比例，控制毛囊干细胞的增殖活性；MAP3K1敲低组（MAP3K1_sh）与过表达组（MAP3K1_OE）的共有差异基因富集于炎症、脂肪细胞分化、急性炎症等GO功能条目。