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从单细胞RNA测序视角看内分泌胰腺的发育与功能障碍

Endocrine Pancreas Development and Dysfunction Through the Lens of Single-Cell RNA-Sequencing.

作者信息

Szlachcic Wojciech J, Ziojla Natalia, Kizewska Dorota K, Kempa Marcelina, Borowiak Malgorzata

机构信息

Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States.

出版信息

Front Cell Dev Biol. 2021 Apr 29;9:629212. doi: 10.3389/fcell.2021.629212. eCollection 2021.

DOI:10.3389/fcell.2021.629212
PMID:33996792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8116659/
Abstract

A chronic inability to maintain blood glucose homeostasis leads to diabetes, which can damage multiple organs. The pancreatic islets regulate blood glucose levels through the coordinated action of islet cell-secreted hormones, with the insulin released by β-cells playing a crucial role in this process. Diabetes is caused by insufficient insulin secretion due to β-cell loss, or a pancreatic dysfunction. The restoration of a functional β-cell mass might, therefore, offer a cure. To this end, major efforts are underway to generate human β-cells , or . The efficient generation of functional β-cells requires a comprehensive knowledge of pancreas development, including the mechanisms driving cell fate decisions or endocrine cell maturation. Rapid progress in single-cell RNA sequencing (scRNA-Seq) technologies has brought a new dimension to pancreas development research. These methods can capture the transcriptomes of thousands of individual cells, including rare cell types, subtypes, and transient states. With such massive datasets, it is possible to infer the developmental trajectories of cell transitions and gene regulatory pathways. Here, we summarize recent advances in our understanding of endocrine pancreas development and function from scRNA-Seq studies on developing and adult pancreas and human endocrine differentiation models. We also discuss recent scRNA-Seq findings for the pathological pancreas in diabetes, and their implications for better treatment.

摘要

长期无法维持血糖稳态会导致糖尿病,糖尿病会损害多个器官。胰岛通过胰岛细胞分泌的激素的协同作用来调节血糖水平,其中β细胞释放的胰岛素在这一过程中起关键作用。糖尿病是由β细胞丢失或胰腺功能障碍导致胰岛素分泌不足引起的。因此,恢复功能性β细胞群可能会提供一种治愈方法。为此,人们正在大力努力生成人类β细胞。高效生成功能性β细胞需要全面了解胰腺发育,包括驱动细胞命运决定或内分泌细胞成熟的机制。单细胞RNA测序(scRNA-Seq)技术的快速发展为胰腺发育研究带来了新的维度。这些方法可以捕获数千个单个细胞的转录组,包括罕见的细胞类型、亚型和瞬时状态。有了如此庞大的数据集,就有可能推断细胞转变的发育轨迹和基因调控途径。在这里,我们总结了从对发育中和成年胰腺以及人类内分泌分化模型的scRNA-Seq研究中,我们对内分泌胰腺发育和功能的理解的最新进展。我们还讨论了糖尿病病理胰腺的最新scRNA-Seq发现及其对更好治疗的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c0/8116659/50dc2440a647/fcell-09-629212-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c0/8116659/ae7db759e8e2/fcell-09-629212-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c0/8116659/50dc2440a647/fcell-09-629212-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c0/8116659/ae7db759e8e2/fcell-09-629212-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c0/8116659/50dc2440a647/fcell-09-629212-g002.jpg

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