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Comparison of epithelial cells from various epithelia and hair follicle stem cells [microarray]

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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 oralmucous, the oesophagusor 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(adult stem cell)的分化潜能在胚胎发育阶段即被限定于特定细胞谱系,其特性受特定微环境(即干细胞龛(niche))调控,并可终生维持。此前学界普遍认为谱系限定是不可逆转的。本研究团队探究了从不同上皮组织中分离的成体干细胞,在暴露于毛发皮肤微环境后是否能够改变其分化命运。研究证实,从多种表达Tp63的组织(如膀胱、口腔黏膜、食管或胸腺)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,可获得全新功能特性。当这些干细胞暴露于毛发皮肤微环境时,便可获得生成毛囊与皮脂腺的能力,从而表现出名副其实的毛发皮肤多能干细胞特性。全基因组筛选分析显示,尽管这些干细胞仍持续表达部分与其起源组织相关的基因,但它们已开始表达毛囊分化相关的典型转录因子。这种分化潜能的提升证明,谱系限定并非不可逆转。

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