Comparison of epithelial cells from various epithelia and hair follicle stem cells

Thepotencyof anadult stem cellisrestricted to certain lineagesduring embryonic life,in response to a specificmicroenvironment (the niche) and it ismaintained for life.Lineage restriction is consideredimmutable.We have investigated if adultstem cells isolated from differentepithelia could change fate by exposing them to ahairy skin niche.We havedemonstrated that clonogenicstem cells restricted to a singleepitheliallineage andculturedfrom various Tp63-expressing tissues e.g, the bladder, the vagina, or the thymuscan acquirenew functionality. When exposed to a hair skinmicroenvironment,thesestem cells acquire thecapacity togeneratehairfolliclesandsebaceous glands,thus behaving likebona fidehairy skinmultipotentstem cells. Genome wide-screen analysis hasdemonstratedthat the stem cellsexpresstranscription factors typical ofhair follicle differentiation,even thoughtheycontinue toexpresssome of thegeneslinked totheirorigin. This increase in potencydemonstrates that lineage restriction is not immutable.成体干细胞的潜能在胚胎发育阶段便被限定于特定细胞谱系，其维持依赖于特定微环境（即干细胞龛(niche)），且这种限定状态将伴随生物体终生。细胞谱系限定曾被认为是不可逆的。我们开展相关研究，旨在探究将不同上皮组织来源的成体干细胞暴露于毛发皮肤龛(hairy skin niche)后，能否改变其细胞命运。实验证实，从多种表达TP63的组织（如膀胱、阴道或胸腺）中分离培养得到的、被限定于单一上皮谱系的克隆形成干细胞(clonogenic stem cells)，能够获得全新的功能特性。当这些干细胞被置于毛发皮肤微环境中时，它们将获得生成毛囊与皮脂腺的能力，表现出名副其实的毛发皮肤多能干细胞(multipotent stem cells)特性。全基因组筛选分析结果显示，这些干细胞会表达毛囊分化相关的典型转录因子，即便它们仍会持续表达部分与其来源组织相关的基因。这种细胞潜能的提升证明，细胞谱系限定并非不可逆的。