《Nature》:胸腺上皮细胞的重新编程

【字体: 时间:2010年08月20日 来源:生物通

编辑推荐:

   英国爱丁堡大学、瑞士洛桑联邦理工学院及洛桑大学医学院组成的研究小组19日宣布在细胞重编程研究方面取得新进展,将胸腺上皮细胞转化成为了皮肤细胞。这一成果将有助于推动器官移植研究。

  

    生物通报道  英国爱丁堡大学、瑞士洛桑联邦理工学院及洛桑大学医学院组成的研究小组19日宣布在细胞重编程研究方面取得新进展,将胸腺上皮细胞转化成为了皮肤细胞。这一成果将有助于推动器官移植研究。该研究成果发表在最新一期《Nature》杂志上。


    该研究小组从大鼠分离获得胸腺上皮细胞(TECs),通过将其置于诱导皮肤微环境中培养使其发生不可逆的命运转变而转化为毛囊多能干细胞。“这些细胞确实完全改变了生命轨迹,他们表达完全不同的基因,这一发现是非常重要的。”洛桑联邦理工学院和洛桑大学医院(CHUV)教授、干细胞动态实验室的负责人Yann Barrandon说。


    在胸腺中,胸腺上皮细胞指导T细胞识别和清除细菌和肿瘤细胞,是免疫系统重要的组成成分。试验显示了在不同的微环境中这些细胞表达不同于原来的遗传标记。但是直到现在,毛囊干细胞维持毛发和皮肤的生长还只取得有限的研究结果。


    Barrandon认为这一发现不但为器官移植和再生领域,而且也为严重烧伤受害者创造了新的机遇。他们同时回应了对于标准生物模型的质疑,证实了不同胚胎起源的细胞分化生成组织的可能性。

(生物通:何嫱)

生物通原文出处推荐

Nature 466, 978-982 (19 August 2010) | doi:10.1038/nature09269; Received 3 August 2009; Accepted 7 June 2010

Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells

Paola Bonfanti, Stéphanie Claudinot, Alessandro W. Amic, Alison Farley, C. Clare Blackburn& Yann Barrandon1,2
The thymus develops from the third pharyngeal pouch of the anterior gut and provides the necessary environment for thymopoiesis (the process by which thymocytes differentiate into mature T lymphocytes) and the establishment and maintenance of self-tolerance1, 2, 3. It contains thymic epithelial cells (TECs) that form a complex three-dimensional network organized in cortical and medullary compartments, the organization of which is notably different from simple or stratified epithelia4. TECs have an essential role in the generation of self-tolerant thymocytes through expression of the autoimmune regulator Aire5, 6, but the mechanisms involved in the specification and maintenance of TECs remain unclear7, 8, 9. Despite the different embryological origins of thymus and skin (endodermal and ectodermal, respectively), some cells of the thymic medulla express stratified-epithelium markers10, 11, 12, interpreted as promiscuous gene expression. Here we show that the thymus of the rat contains a population of clonogenic TECs that can be extensively cultured while conserving the capacity to integrate in a thymic epithelial network and to express major histocompatibility complex class II (MHC II) molecules and Aire. These cells can irreversibly adopt the fate of hair follicle multipotent stem cells when exposed to an inductive skin microenvironment; this change in fate is correlated with robust changes in gene expression. Hence, microenvironmental cues are sufficient here to re-direct epithelial cell fate, allowing crossing of primitive germ layer boundaries and an increase in potency

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