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综合的α,β和delta细胞转录学揭示了细胞衰老与MHC I类上调调节的关联

W Staels¹, C Berthault², S Bourgeois³

¹Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, France; Genetics, Reproduction and Development (GRAD), Vrije Universiteit Brussel (VUB), Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.

Molecular metabolism

|July 15, 2024

概括

一种新的细胞净化方法有效地隔离了所有年龄段的小鼠胰腺α,β和delta细胞. 衰老显示细胞循环减少和炎症的签名,影响免疫反应和潜在的糖尿病.

科学领域:

内分泌学在内分泌学.
细胞生物学细胞生物学
衰老研究研究衰老研究

背景情况:

胰腺小岛含有对代谢调节至关重要的α,β和delta细胞.
了解这些细胞的与年龄相关的变化对于解决糖尿病和免疫功能障碍至关重要.
目前用于隔离不同年龄段的特定岛屿细胞类型的现有方法有限.

研究的目的:

验证一种基于FACS的净化方法,用于来自不同年龄 (新生儿,成年人,老年人) 的老鼠小岛的α,β和delta细胞.
在整个产后发育过程中研究这些纯化的细胞群中的转录组动力学.
在小鼠胰腺内分泌细胞中识别与年龄相关的转录变化.

主要方法:

光激活细胞分类 (FACS) 使用CD71和CD24标记物来净化α,β和delta细胞.
将净化方法应用于新生 (1周),成年 (12周) 和老年 (18个月) 小鼠的小岛.
大量RNA测序和生物信息分析 (差异基因表达,过度代表,交叉分析) 纯化的细胞群.

主要成果:

从所有测试年龄的小鼠中成功净化FACS的α,β和delta细胞,使用单一的方法.
转录组分析显示,从新生儿到成年小鼠的过渡期间,细胞循环减少和神经元类特征增加.
在老化的α,β和delta细胞中发现了一种炎症特征,其特征是增加β-2微球蛋白和MHC I类表达,在老化的α,β和delta细胞中发现了炎症特征.

结论:

开发的细胞分类技术对于在不同年龄段净化小鼠胰腺内分泌细胞子集是有效的.
这项研究为了解胰腺内分泌衰老提供了宝贵的资源.
衰老的α,β和delta细胞中的炎症特征表明对免疫调节和与年龄相关的糖尿病有影响.

关键词:

一个阿尔法细胞的细胞.贝塔细胞是贝塔细胞.达尔塔细胞是什么?在MHC I类中,MHC是I类.成熟成熟成熟成熟成熟胰腺小岛是一个胰腺小岛.

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