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新方法揭示单细胞转录组与人类胰岛失调的关联
2020-04-19 12:55

加拿大阿尔伯塔大学Patrick E. MacDonald、美国斯坦福大学Stephen R. Quake、Seung K. Kim等研究人员合作,利用新方法揭示了单细胞转录组与人类胰岛失调的关联。相关论文于2020年4月16日在线发表在《细胞—代谢》杂志上。

研究人员发现,单细胞RNA测序与胞吐作用和通道活性的电生理测量联合(patch-seq)可用于在单细胞水平上链接内分泌生理学和转录组。研究人员从34位有/无糖尿病的人类供体胰腺中收集了1369个patch-seq细胞。对功能和基因表达网络的分析确定了与β细胞中功能异质性相关的基因集,从而可用于预测电生理。
 
研究人员还报告了2型糖尿病功能障碍的转录程序,并将这种方法扩展至1型糖尿病供体的冷冻保存细胞,从而为了解健康和疾病中的胰岛细胞异质性提供了宝贵资源。
 
据了解,胰岛细胞功能受损是人类代谢失调和疾病的主要原因。尽管如此,直接将胰岛细胞的生理功能障碍与基因表达的精确变化联系起来仍然具有挑战性。
 
附:英文原文

Title: Patch-Seq Links Single-Cell Transcriptomes to Human Islet Dysfunction in Diabetes

Author: Joan Camunas-Soler, Xiao-Qing Dai, Yan Hang, Austin Bautista, James Lyon, Kunimasa Suzuki, Seung K. Kim, Stephen R. Quake, Patrick E. MacDonald

Issue&Volume: 2020-04-16

Abstract: Impaired function of pancreatic islet cells is a major cause of metabolic dysregulationand disease in humans. Despite this, it remains challenging to directly link physiologicaldysfunction in islet cells to precise changes in gene expression. Here we show thatsingle-cell RNA sequencing combined with electrophysiological measurements of exocytosisand channel activity (patch-seq) can be used to link endocrine physiology and transcriptomesat the single-cell level. We collected 1,369 patch-seq cells from the pancreata of34 human donors with and without diabetes. An analysis of function and gene expression networksidentified a gene set associated with functional heterogeneity in β cells that canbe used to predict electrophysiology. We also report transcriptional programs underlyingdysfunction in type 2 diabetes and extend this approach to cryopreserved cells fromdonors with type 1 diabetes, generating a valuable resource for understanding isletcell heterogeneity in health and disease.

DOI: 10.1016/j.cmet.2020.04.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30187-X

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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