成年干細(xì)胞維持我們身體組織的正常穩(wěn)定狀態(tài),,并且負(fù)責(zé)受傷組織修復(fù),。這些細(xì)胞通常位于特殊的小生境(niche)中,合適的微環(huán)境使得干細(xì)胞保持復(fù)制和組織再生能力,。在哺乳動物毛囊中,,成體干細(xì)胞">成體干細(xì)胞以相對靜止的狀態(tài)位于毛囊峽部(bulge),它們對于毛發(fā)生長非常重要,。小鼠毛囊干細(xì)胞能形成所有3種皮膚上皮細(xì)胞系,,而在正常狀態(tài)下,這些干細(xì)胞會周期性的激活,,以促進(jìn)初生毛發(fā)生長,。
盡管所有毛囊在小鼠出生時(shí)已經(jīng)開始發(fā)育,但是毛囊峽部微環(huán)境在出生后3周仍不顯著,,此時(shí)小鼠已經(jīng)具有完整的表皮毛發(fā)覆蓋,。因此,毛囊干細(xì)胞從何而來,,它們是如何形成微結(jié)構(gòu)的尚不清楚,。此前,科學(xué)家認(rèn)為這些細(xì)胞對于胚胎發(fā)育并非必需,,因?yàn)槊襾碜杂诒砥?,而不是峽部微環(huán)境,。為了研究毛囊干細(xì)胞是否在發(fā)育早期就已經(jīng)存在,以及其是否發(fā)揮作用,,來自美國洛克菲勒大學(xué)的一組科學(xué)家進(jìn)行了相關(guān)研究,,并將結(jié)果發(fā)表在2008年7月3日出版的《細(xì)胞—干細(xì)胞》(Cell Stem Cell)上。
毛囊干細(xì)胞有多種標(biāo)記物,,這些標(biāo)記物能幫助研究人員了解干細(xì)胞的特征和行為等,。其中包括廣泛應(yīng)用的CD34,以及轉(zhuǎn)錄因子Lhx2,、Sox9,、Tcf3、Nfatc1等,。與CD34不同的是,這些轉(zhuǎn)錄因子的表達(dá)開始于毛囊形成時(shí)期,。在研究中,,科學(xué)家利用了基因技術(shù)、細(xì)胞生物技術(shù)等對毛囊干細(xì)胞進(jìn)行了分析,。結(jié)果發(fā)現(xiàn),,慢周期細(xì)胞(slow-cycling cell)在皮膚發(fā)育早期就已經(jīng)出現(xiàn),并且表達(dá)干細(xì)胞標(biāo)記物,,接著形成成年干細(xì)胞,。為了測試這些早期的慢周期細(xì)胞是否起到了干細(xì)胞作用,研究小組利用Sox9-Cre作為基因標(biāo)記,,實(shí)驗(yàn)結(jié)果表明,,表達(dá)Sox9的細(xì)胞最后能形成所有皮膚上皮細(xì)胞系,而Sox9對于干細(xì)胞分化是必需的,。
因此,,毛囊干細(xì)胞在毛囊形成最早期階段就發(fā)生分化,并且初期的干細(xì)胞分化依賴于Sox9,。更重要的是,,早期的毛囊干細(xì)胞對于3種皮膚上皮細(xì)胞系形成都有貢獻(xiàn),一旦缺少這些細(xì)胞,,毛囊和皮脂腺的正常形態(tài)發(fā)生就會受到阻礙,,而同時(shí)上皮損傷修復(fù)也會被影響。
新研究結(jié)果證實(shí)了早期毛囊干細(xì)胞的存在,,并且表明了它們在組織形態(tài)發(fā)生過程中的重要生理作用,。(生物谷Bioon.com)
生物谷推薦原始出處:
Cell Stem Cell,Vol 3, 33-43, 03 July 2008,,Jonathan A. Nowak, Elaine Fuchs
Hair Follicle Stem Cells Are Specified and Function in Early Skin Morphogenesis
Jonathan A. Nowak,1 Lisa Polak,1 H. Amalia Pasolli,1 and Elaine Fuchs1,
1 Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA
Corresponding author
Elaine Fuchs
[email protected]
Summary
In adult skin, epithelial hair follicle stem cells (SCs) reside in a quiescent niche and are essential for cyclic bouts of hair growth. Niche architecture becomes pronounced postnatally at the start of the first hair cycle. Whether SCs exist or function earlier is unknown. Here we show that slow-cycling cells appear early in skin development, express SC markers, and later give rise to the adult SC population. To test whether these early slow-cycling cells function as SCs, we use Sox9-Cre for genetic marking and K14-Cre to embryonically ablate Sox9, an essential adult SC gene. We find that the progeny of Sox9-expressing cells contribute to all skin epithelial lineages and Sox9 is required for SC specification. In the absence of early SCs, hair follicle and sebaceous gland morphogenesis is blocked, and epidermal wound repair is compromised. These findings establish the existence of early hair follicle SCs and reveal their physiological importance in tissue morphogenesis.