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DUSP6 抑制毛囊干细胞(HFSCs)的增殖。

DUSP6 inhibits the proliferation of hair follicle stem cells (HFSCs) .

机构信息

Key Laboratory for Animal Genetics & Molecular Breeding of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

出版信息

Anim Biotechnol. 2023 Nov;34(4):1223-1231. doi: 10.1080/10495398.2021.2016433. Epub 2022 Jan 4.

Abstract

RNA-seq has shown that the DUSP6 and MAPK signaling pathways are associated with the production of high-quality brush hair (type III hair) in Yangtze River Delta white goats. However, there are few reports on the regulatory effects of DUSP6 expression on hair follicle stem cells (HFSCs) and cellular processes, as well as the underlying mechanism. Here, we investigated the effect of DUSP6 level in HFSCs and the molecular mechanism underlying the functional regulation of HFSCs by DUSP6. Overexpression of DUSP6 significantly suppressed the proliferation of HFSCs by inducing cell cycle arrest in the G1 phase and by promoting apoptosis. Transcriptome analysis revealed a total of 217 differentially expressed genes between DUSP6-overexpressing and control HFSCs, of which 33 (15.2%) were upregulated in DUSP6-overexpressing cells. The two pathways with the most significant enrichment of differentially expressed genes were the TNF signaling pathway and cytokine-cytokine receptor interaction pathway, and the significantly enriched terms in the GO enrichment analysis involved cell attachment and cytokines. These results indicate that DUSP6 can function as an inhibitory factor in HFSCs through the induction of cell cycle arrest in the G1 phase and can promote apoptosis by mediating crosstalk among several pathways and cytokines.HighlightsWe constructed DUSP6 overexpression vectors to detect mRNA and protein expression levels related to high-quality brush hair in MAPK signaling pathway.We found that high expression level of DUSP6 can inhibit the proliferation of hair follicle stem cells (HFSCs) and promote cell apoptosis of HFSCs.DUSP6 may be involved in the growth regulation of HFSCs like Other studies in cancer, tumors by regulating the expression of cytokines, changing the transmission of signals between cells, activating or suppressing immune-related pathways.

摘要

RNA-seq 研究表明,DUSP6 和 MAPK 信号通路与长三角白山羊高质量刷状毛(III 型毛)的产生有关。然而,关于 DUSP6 表达对毛囊干细胞(HFSCs)和细胞过程的调节作用及其潜在机制的报道较少。在这里,我们研究了 DUSP6 水平在 HFSCs 中的作用,以及 DUSP6 对 HFSCs 功能调节的潜在分子机制。过表达 DUSP6 通过诱导 G1 期细胞周期停滞和促进细胞凋亡,显著抑制 HFSCs 的增殖。转录组分析显示,DUSP6 过表达和对照 HFSCs 之间共有 217 个差异表达基因,其中 33 个(15.2%)在 DUSP6 过表达细胞中上调。差异表达基因富集度最高的两个通路是 TNF 信号通路和细胞因子-细胞因子受体相互作用通路,GO 富集分析中显著富集的术语涉及细胞附着和细胞因子。这些结果表明,DUSP6 可以通过诱导 G1 期细胞周期停滞作为 HFSCs 的抑制因子发挥作用,并通过介导几个通路和细胞因子之间的串扰促进细胞凋亡。

亮点

我们构建了 DUSP6 过表达载体,以检测 MAPK 信号通路中与高质量刷状毛相关的 mRNA 和蛋白表达水平。

我们发现,DUSP6 的高表达水平可以抑制毛囊干细胞(HFSCs)的增殖,促进 HFSCs 的细胞凋亡。

DUSP6 可能通过调节细胞因子的表达、改变细胞间信号的传递、激活或抑制免疫相关通路,参与 HFSCs 的生长调节,就像其他癌症、肿瘤研究一样。

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