Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.
Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging.
Project description:Hair follicle stem cells(HFSCs) can transition between active and quiescent stages during normal hair cycle or would healing. Transcriptional regulation has been show to regulate the transition. Previous studies have shown that two transcription factor, Foxc1 and Nfatc1, can help maintain the stem cells in quiescent state, the deletion of either one could lead to precocious activation. Here, we collect the hair follicle stem cell at postnatal day 30 from both control mice, Nfatc1 knockout mice, Foxc1 knockout mice(downloaded) and Foxc1/Nfatc1 double knockout mice to study the transcriptional regulation network of HFSCs quiescence.
Project description:Long-term adult stem cells sustain tissue homeostasis and regeneration throughout the lifetime of an organism. They are thought to originate from embryonic progenitors that acquired long-term self-renewal ability and multipotency at the end of organogenesis. We aim to mechanistically understand the embryonic origin of localized hair follicle stem cells. Here we discover embryonic progenitor cells occupying upper hair peg location; expressing a stem cell marker Nfatc1, contribute to long-term hair follicle stem cells, while the ones locating in the lower hair peg, expressing Shh, acquire differentiated cell fate. To understand the underlying mechanism leading to niche-induced HFSC specification, we profiled the expression of mRNA isolated from purified hair peg cells expressing Shh or Nfatc1. Based on DAVID functional gene annotation analysis, among genes that were expressed 2 fold more in Shh+ cells than in Nfatc1+ cells, we found that genes of the Wnt signaling pathway were enriched prominently. Base on these result and further genetic study, we suggest when hair placode develops to hair peg, a localized Wnt/β-catenin signal free zone emerges. Embryonic progenitors residing in this region gain expression of stem cell markers compared to their precursors and become definitive long-term hair follicle stem cells.