Patch-Seq Links Single-Cell Transcriptomes to Human Islet Dysfunction in Diabetes
Patch-Seq Links Single-Cell Transcriptomes to Human Islet Dysfunction in Diabetes
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DOI：
10.1016/j.cmet.2020.04.005
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发表时间：
2020-05-05
期刊：
影响因子：
29
通讯作者：
MacDonald, Patrick E.
中科院分区：
文献类型：
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作者：
Camunas-Soler, Joan;Dai, Xiao-Qing;MacDonald, Patrick E.
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，将胰岛细胞的生理功能障碍与基因表达的精确变化直接联系起来仍然具有挑战性。在这里，我们表明，单细胞RNA测序结合胞吐和通道活性的电生理测量（patch-seq）可用于在单细胞水平上连接内分泌生理学和转录组。我们从34名患有和不患有糖尿病的人类供体的胰腺中收集了1，369个patch-seq细胞。对功能和基因表达网络的分析鉴定了与B细胞中的功能异质性相关的基因集，其可用于预测电生理学。我们还报告了2型糖尿病功能障碍的转录程序，并将这种方法扩展到1型糖尿病供体的冻存细胞，为了解健康和疾病中的胰岛细胞异质性提供了宝贵的资源。
Impaired function of pancreatic islet cells is a major cause of metabolic dysregulation and disease in humans. Despite this, it remains challenging to directly link physiological dysfunction in islet cells to precise changes in gene expression. Here we show that single-cell RNA sequencing combined with electrophysiological measurements of exocytosis and channel activity (patch-seq) can be used to link endocrine physiology and transcriptomes at the single-cell level. We collected 1,369 patch-seq cells from the pancreata of 34 human donors with and without diabetes. An analysis of function and gene expression networks identified a gene set associated with functional heterogeneity in b cells that can be used to predict electrophysiology. We also report transcriptional programs underlying dysfunction in type 2 diabetes and extend this approach to cryopreserved cells from donors with type 1 diabetes, generating a valuable resource for understanding islet cell heterogeneity in health and disease.