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具有差异性功能的内分泌小岛β细胞亚型来自生物化学上不同的胚胎内分泌小岛前代,这些前代受母体营养素的调节

Guoqiang Gu¹, Monica Brown¹, Verda Agan¹

¹Vanderbilt University.

Research square

|March 18, 2024

概括

胚胎小岛的祖先会产生不同的β细胞亚型,具有不同的功能和活力. 孕产妇过度营养会损害这一过程,影响糖尿病风险,并通过表观遗传修饰提供治疗途径.

科学领域:

内分泌学在内分泌学.
发展生物学发展生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

内分泌岛屿β细胞是异质的,但它们的发育起源和稳定性尚不清楚.
了解β细胞子集的发展对于预防和治疗糖尿病至关重要,因为数量减少和功能受损会增加疾病风险.

研究的目的:

研究不同内分泌岛屿β细胞亚型的发育起源和稳定性.
探索基因表达,DNA甲基化和母体营养在β细胞子集分化和功能中的作用.

主要方法:

组合细胞谱系的追踪.
单细胞RNA测序 (scRNA-seq) 是一种
对DNA甲基化分析进行分析.

主要成果:

具有明显表观遗传和转录基因特征的胚胎岛屿祖先在成年小鼠中产生功能上不同的β细胞亚型.
一种高功能的β细胞亚型的特点是丰富了参与分泌,应激反应和信号传递的基因,与相应的差异性DNA甲基化有关.
孕产妇过度营养会破坏DNA甲基转移酶3a,减少高功能的β细胞祖先的比例.
已识别的小鼠β细胞亚型特征准确地分类了人类细胞,并揭示了糖尿病捐赠者的高功能β细胞减少.

结论:

不同的β细胞亚型来自表观遗传学和转录学上不同的胚胎原始体.
孕产妇的营养通过表观遗传机制显著影响β细胞的发育和功能,影响糖尿病风险.
针对小岛祖先的DNA甲基化,可能通过母体补充剂,可能是糖尿病预防和治疗的策略.

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