小柯机器人

德国马克斯普朗克免疫生物学和表观遗传学研究所John Andrew Pospisilik和Erez Dror共同合作，近期取得重要工作进展。他们研究发现，表观遗传剂量可以确定两种主要且功能不同的β细胞亚型。相关研究成果2023年3月21日在线发表于《细胞—代谢》杂志上。

据介绍，指定和稳定细胞亚型的机制仍知之甚少。

研究人员根据组蛋白标记的异质性确定了胰腺β细胞的两种主要亚型（β_HI和β_LO）。β_HI细胞表现出高出约4倍的H3K27me3水平，独特的染色质组织和致密化，以及特定的转录模式。β_HI和β_LO细胞在大小、形态、胞浆和细胞核超微结构、表观基因组、细胞表面标记物表达和功能方面也不同，并且可以通过FACS分离为CD24⁺和CD24⁻的部分。在功能上，β_HI细胞在体内和体外都增加了线粒体的质量、活性和胰岛素分泌。

功能的部分丧失表明H3K27me3剂量可在体内调节β_HI/β_LO的比率，这表明对β细胞亚型特征和比率的控制至少部分解耦。这两种亚型在人类中都是保守的，β_HI细胞在2型糖尿病患者中富集。

因此，表观遗传学剂量是细胞亚型规范的新型调节剂，可识别两种功能不同的β细胞亚型。

附：英文原文

Title: Epigenetic dosage identifies two major and functionally distinct β cell subtypes

Author: Erez Dror, Luca Fagnocchi, Vanessa Wegert, Stefanos Apostle, Brooke Grimaldi, Tim Gruber, Ilaria Panzeri, Steffen Heyne, Kira Daniela Hffler, Victor Kreiner, Reagan Ching, Tess Tsai-Hsiu Lu, Ayush Semwal, Ben Johnson, Parijat Senapati, Adelheid Lempradl, Dustin Schones, Axel Imhof, Hui Shen, John Andrew Pospisilik

Issue&Volume: 2023-03-21

Abstract: The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (βHI and βLO). βHI cells exhibit ～4-fold higher levels of H3K27me3, distinct chromatin organization and compaction, and a specific transcriptional pattern. βHI and βLO cells also differ in size, morphology, cytosolic and nuclear ultrastructure, epigenomes, cell surface marker expression, and function, and can be FACS separated into CD24+ and CD24 fractions. Functionally, βHI cells have increased mitochondrial mass, activity, and insulin secretion in vivo and ex vivo. Partial loss of function indicates that H3K27me3 dosage regulates βHI/βLO ratio in vivo, suggesting that control of β cell subtype identity and ratio is at least partially uncoupled. Both subtypes are conserved in humans, with βHI cells enriched in humans with type 2 diabetes. Thus, epigenetic dosage is a novel regulator of cell subtype specification and identifies two functionally distinct β cell subtypes.

DOI: 10.1016/j.cmet.2023.03.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00086-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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