通过感应葡萄糖的胰岛素分泌的人类α细胞在小鼠中缓解糖尿病
Kenichiro Furuyama1, Simona Chera1,2, Léon van Gurp1
1Department of Genetic Medicine and Development, iGE3 and Centre Facultaire du Diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Nature
|February 15, 2019
概括
人类小岛细胞可以转换身份成为产生胰岛素的细胞, 人类胰腺细胞的可塑性为再生医学提供了希望.
科学领域:
- 内分泌学
- 复原医学
- 细胞生物学
背景情况:
- 细胞身份切换是动物已知的再生策略,但对哺乳动物的理解很少.
- 在小鼠中,胰腺α和delta细胞可以在β细胞丧失后转化为产生胰岛素的β细胞.
- 人类小岛细胞的可塑性,特别是在糖尿病中,仍然很大程度上是未知的.
研究的目的:
- 调查人类小岛非β细胞 (α和gamma细胞) 是否具有可塑性.
- 确定这些人体细胞是否可以被重新编程产生胰岛素.
- 评估转化人类小岛细胞在糖尿病治疗中的治疗潜力.
主要方法:
- 来自非糖尿病患者和糖尿病患者的人类小岛细胞的血统追踪.
- 使用转录因子PDX1和MAFA重新编程非β细胞 (生产alpha和PPY的玛细胞).
- 将转化细胞移植到糖尿病小鼠中,并对胰岛素的产生和糖尿病的逆转进行评估.
- 对转换的产生胰岛素的α细胞进行了深度转录和蛋白质分析.
主要成果:
- 人类小岛的α和gamma细胞成功地被重新编程,以产生和分泌胰岛素作为对葡萄糖的反应.
- 移植的转化人类α细胞在小鼠中逆转了糖尿病,并维持了至少6个月的胰岛素产生.
- 重编程的阿尔法细胞保留了阿尔法细胞标记的表达,表明稳定的细胞身份.
- 深度分子表征证实了转化细胞的可塑性和功能.
结论:
- 人类小岛细胞具有可塑性,允许非β细胞转化为功能性胰岛素产生细胞.
- 这种细胞重编程为通过再生医学治疗糖尿病提供了一个有希望的途径.
- 这些发现为了解和利用现场细胞可塑性来治疗糖尿病和其他退行性疾病提供了分子框架.
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