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单细胞多组和空间分析揭示了胰腺细胞类型特定的1型糖尿病进展的基因调控程序

Rebecca Melton¹, Sara Jimenez², Weston Elison¹

¹Biomedical Sciences Program, University of California San Diego, La Jolla, CA, USA.

Science advances

|September 10, 2025

概括

研究人员使用先进的多组学研究了1型糖尿病 (T1D) 中的胰腺细胞变化. 他们确定了驱动T1D的关键细胞和信号改变,揭示了疾病预防的潜在治疗点.

科学领域:

内分泌学在内分泌学.
免疫学免疫学免疫学
基因组学就是基因组学.

背景情况:

在胰腺1型糖尿病 (T1D) 中,细胞类型特定的调节机制尚不清楚.
了解这些机制对于制定有效的T1D预防和治疗策略至关重要.

研究的目的:

在T1D进展过程中调查胰腺中细胞类型特定的调节程序.
确定与T1D发展和风险相关的分子驱动因素和细胞变化.

主要方法:

单核多组学和空间转录组学用于非糖尿病,自身抗体阳性和T1D捐赠者的胰腺样本.
在12种胰腺细胞类型中对超过85万个细胞进行了基因组分析.

主要成果:

在T1D进展过程中,在β细胞,细胞和其他胰腺细胞类型中观察到改变的丰度和基因活性.
与T1D患者相比,在自身抗体阳性个体中受到了不同的途径的影响.
表观基因驱动因素和遗传关联揭示了T1D风险的因果途径,包括β细胞中的抗原呈现.
单细胞和空间数据表明,细胞信号传递的广泛变化影响β细胞调节.

结论:

这项研究揭示了胰腺T1D的关键细胞和分子驱动因素.
已识别的途径和信号改变为T1D预防提供了新的治疗点的基础.

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