2012年9月7日 訊 /生物谷BIOON/ 睪丸支持細(xì)胞（Sertoli cells）被認(rèn)為是在胚胎發(fā)育階段性別決定和在成年期精子發(fā)生中，起著至關(guān)重要的作用,。它們?cè)谀行陨芰χ兴哂械闹匾饔?，以及其抑制免疫特性和神?jīng)營養(yǎng)特性，使它們?cè)谂R床應(yīng)用上具有廣闊的前景,。
在本研究中,，美國麻省理工學(xué)院的研究者，在成纖維細(xì)胞中表達(dá)五個(gè)轉(zhuǎn)錄因子,，生成了誘導(dǎo)胚胎塞爾托利樣細(xì)胞（Sertoli-like cells ,ieSCs）,。
研究者證實(shí)了該特定轉(zhuǎn)錄因子組合，在成纖維細(xì)胞向ieSCs轉(zhuǎn)變過程中的作用,，并確定了在這個(gè)過程中的幾個(gè)關(guān)鍵步驟,。
最初，發(fā)生轉(zhuǎn)變的成纖維細(xì)胞進(jìn)行了從間充質(zhì)細(xì)胞向上皮細(xì)胞的轉(zhuǎn)變,，然后獲得了聚集的能力,，并形成管狀結(jié)構(gòu)，表達(dá)胚胎睪丸支持細(xì)胞的特定標(biāo)記物,。
這些睪丸支持細(xì)胞樣細(xì)胞（Sertoli-like cells）,，可促進(jìn)神經(jīng)細(xì)胞的分化和神經(jīng)前體細(xì)胞（NPCs）自我更新，支持體外培養(yǎng)中的生殖細(xì)胞的生存,，與內(nèi)源性胚胎Sertoli細(xì)胞和原始生殖細(xì)胞相協(xié)同,，促進(jìn)產(chǎn)生胎兒性腺睪丸索。
總之,，該研究在促進(jìn)治療男性不育癥,，以及胚胎生殖發(fā)育研究等多個(gè)方面都具有重大的意義,。（生物谷bioon.com）
doi:10.1016/j.stem.2012.07.019
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Direct Reprogramming of Fibroblasts into Embryonic Sertoli-like Cells by Defined Factors
Yosef Buganim, Elena Itskovich, Yueh-Chiang Hu, Albert W. Cheng, Kibibi Ganz, Sovan Sarkar, Dongdong Fu, G. Grant Welstead, David C. Page, Rudolf Jaenisch
Sertoli cells are considered the supporting cells of the testis that play an essential role in sex determination during embryogenesis and in spermatogenesis during adulthood. Their essential roles in male fertility along with their immunosuppressive and neurotrophic properties make them an attractive cell type for therapeutic applications. Here we demonstrate the generation of induced embryonic Sertoli-like cells (ieSCs) by ectopic expression of five transcription factors. We characterize the role of specific transcription factor combinations in the transition from fibroblasts to ieSCs and identify key steps in the process. Initially, transduced fibroblasts underwent a mesenchymal to epithelial transition and then acquired the ability to aggregate, formed tubular-like structures, and expressed embryonic Sertoli-specific markers. These Sertoli-like cells facilitated neuronal differentiation and self-renewal of neural progenitor cells (NPCs), supported the survival of germ cells in culture, and cooperated with endogenous embryonic Sertoli and primordial germ cells in the generation of testicular cords in the fetal gonad.
