Comprehensive alpha, beta, and delta cell transcriptomics reveal an association of cellular aging with MHC class I upregulation

IF 7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2024-07-14 DOI:10.1016/j.molmet.2024.101990

W. Staels , C. Berthault , S. Bourgeois , V. Laville , C. Lourenço , N. De Leu , R. Scharfmann

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引用次数: 0

Abstract

Objectives

This study aimed to evaluate the efficacy of a purification method developed for isolating alpha, beta, and delta cells from pancreatic islets of adult mice, extending its application to islets from newborn and aged mice. Furthermore, it sought to examine transcriptome dynamics in mouse pancreatic endocrine islet cells throughout postnatal development and to validate age-related alterations within these cell populations.

Methods

We leveraged the high surface expression of CD71 on beta cells and CD24 on delta cells to FACS-purify alpha, beta, and delta cells from newborn (1-week-old), adult (12-week-old), and old (18-month-old) mice. Bulk RNA sequencing was conducted on these purified cell populations, and subsequent bioinformatic analyses included differential gene expression, overrepresentation, and intersection analysis.

Results

Alpha, beta, and delta cells from newborn and aged mice were successfully FACS-purified using the same method employed for adult mice. Our analysis of the age-related transcriptional changes in alpha, beta, and delta cell populations revealed a decrease in cell cycling and an increase in neuron-like features processes during the transition from newborn to adult mice. Progressing from adult to old mice, we identified an inflammatory gene signature related to aging (inflammaging) encompassing an increase in β-2 microglobulin and major histocompatibility complex (MHC) Class I expression.

Conclusions

Our study demonstrates the effectiveness of our cell sorting technique in purifying endocrine subsets from mouse islets at different ages. We provide a valuable resource for better understanding endocrine pancreas aging and identified an inflammaging gene signature with increased β-2 microglobulin and MHC Class I expression as a common hallmark of old alpha, beta, and delta cells, with potential implications for immune response regulation and age-related diabetes.

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全面的α、β和δ细胞转录组学揭示了细胞衰老与 MHC I 类上调之间的关联。

研究目的本研究旨在评估从成年小鼠胰岛中分离α、β和δ细胞的纯化方法的有效性，并将其应用扩展到新生小鼠和老龄小鼠的胰岛。此外，它还试图研究小鼠胰腺内分泌胰岛细胞在整个出生后发育过程中的转录组动态，并验证这些细胞群中与年龄相关的变化：方法：我们利用β细胞表面高表达的CD71和δ细胞表面高表达的CD24，从新生小鼠（1周大）、成年小鼠（12周大）和老龄小鼠（18个月大）的α、β和δ细胞中进行FACS纯化。对这些纯化的细胞群进行了大量 RNA 测序，随后进行了生物信息学分析，包括差异基因表达、过度代表和交叉分析：结果：采用与成年小鼠相同的方法，成功地对新生小鼠和老年小鼠的α、β和δ细胞进行了FACS纯化。我们对α、β和δ细胞群中与年龄相关的转录变化进行的分析表明，在新生小鼠向成年小鼠过渡的过程中，细胞周期减少，神经元样特征过程增加。从成年小鼠到老年小鼠，我们发现了与衰老（炎症老化）有关的炎症基因特征，包括β-2微球蛋白和主要组织相容性复合体（MHC）I类表达的增加：我们的研究证明了细胞分拣技术在纯化不同年龄小鼠胰岛内分泌亚群方面的有效性。我们为更好地了解胰腺内分泌衰老提供了宝贵的资源，并确定了一种炎症基因特征，即β-2微球蛋白和MHC I类表达的增加是老年α、β和δ细胞的共同特征，这对免疫反应调节和年龄相关性糖尿病具有潜在的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.