关键词:重编程,男性不育症,成纤维细胞,睾丸支持细胞,精子发生
2012年9月7日 讯 /生物谷BIOON/ 睾丸支持细胞(Sertoli cells)被认为是在胚胎发育阶段性别决定和在成年期精子发生中,起着至关重要的作用。它们在男性生育能力中所具有的重要作用,以及其抑制免疫特性和神经营养特性,使它们在临床应用上具有广阔的前景。
在本研究中,美国麻省理工学院的研究者,在成纤维细胞中表达五个转录因子,生成了诱导胚胎塞尔托利样细胞(Sertoli-like cells ,ieSCs)。
研究者证实了该特定转录因子组合,在成纤维细胞向ieSCs转变过程中的作用,并确定了在这个过程中的几个关键步骤。
最初,发生转变的成纤维细胞进行了从间充质细胞向上皮细胞的转变,然后获得了聚集的能力,并形成管状结构,表达胚胎睾丸支持细胞的特定标记物。
这些睾丸支持细胞样细胞(Sertoli-like cells),可促进神经细胞的分化和神经前体细胞(NPCs)自我更新,支持体外培养中的生殖细胞的生存,与内源性胚胎Sertoli细胞和原始生殖细胞相协同,促进产生胎儿性腺睾丸索。
总之,该研究在促进治疗男性不育症,以及胚胎生殖发育研究等多个方面都具有重大的意义。(生物谷bioon.com)
doi:10.1016/j.stem.2012.07.019
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PMID:
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.
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