期刊
STEM CELLS
卷 34, 期 9, 页码 2407-2417出版社
WILEY
DOI: 10.1002/stem.2418
关键词
Differentiation; Epidermis; Hair follicle stem cells; Histone; Jun
资金
- UGC fellowship
- ACTREC fellowship
- ICMR, India
Secretory phospholipase A(2) Group-IIA (sPLA(2)-IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA(2)-IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA(2)-IIA (K14-sPLA(2)-IIA) showed depletion of HFSC pool. This was accompanied with increased differentiation, loss of ortho-parakeratotic organization and enlargement of sebaceous gland, infundibulum and junctional zone. The colony forming efficiency of keratinocytes was significantly reduced. Microarray profiling of HFSCs revealed enhanced level of epithelial mitogens and transcription factors, c-Jun and FosB that may be involved in proliferation and differentiation. Moreover, K14-sPLA(2)-IIA keratinocytes showed enhanced activation of EGFR and JNK1/2 that led to c-Jun activation, which co-related with enhanced differentiation. Further, depletion of stem cells in bulge is associated with high levels of chromatin silencing mark, H3K27me3 and low levels of an activator mark, H3K9ac suggestive of alteration in gene expression contributing toward stem cells differentiation. Our results, first time uncovered that overexpression of sPLA(2)-IIA lead to depletion of HFSCs and differentiation associated with altered histone modification. Thus involvement of sPLA(2)-IIA in stem cells regulation and disease pathogenesis suggest its prospective clinical implications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据