Departments of Pediatrics and Cellular & Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
Mol Metab. 2017 May 5;6(9):991-1001. doi: 10.1016/j.molmet.2017.04.012. eCollection 2017 Sep.
Blood glucose levels are tightly controlled by the coordinated actions of hormone-producing endocrine cells that reside in pancreatic islets. Islet cell malfunction underlies diabetes development and progression. Due to the cellular heterogeneity within islets, it has been challenging to uncover how specific islet cells contribute to glucose homeostasis and diabetes pathogenesis. Recent advances in single-cell technologies and computational methods have opened up new avenues to resolve islet heterogeneity and study islet cell states in health and disease.
In the past year, a multitude of studies have been published that used single-cell approaches to interrogate the transcriptome and proteome of the different islet cell types. Here, we summarize the conclusions of these studies, as well as discuss the technologies used and the challenges faced with computational analysis of single-cell data from islet studies.
By analyzing single islet cells from rodents and humans at different ages and disease states, the studies reviewed here have provided new insight into endocrine cell function and facilitated a high resolution molecular characterization of poorly understood processes, including regeneration, maturation, and diabetes pathogenesis. Gene expression programs and pathways identified in these studies pave the way for the discovery of new targets and approaches to prevent, monitor, and treat diabetes.
血糖水平受到位于胰岛中的激素产生内分泌细胞的协调作用的严格控制。胰岛细胞功能障碍是糖尿病发展和进展的基础。由于胰岛内的细胞异质性,揭示特定胰岛细胞如何有助于葡萄糖稳态和糖尿病发病机制一直具有挑战性。单细胞技术和计算方法的最新进展为解决胰岛异质性以及在健康和疾病中研究胰岛细胞状态开辟了新途径。
在过去的一年中,已经发表了许多使用单细胞方法来研究不同胰岛细胞类型的转录组和蛋白质组的研究。在这里,我们总结了这些研究的结论,并讨论了用于研究胰岛的单细胞数据的计算分析所面临的技术和挑战。
通过分析来自不同年龄和疾病状态的啮齿动物和人类的单个胰岛细胞,这里综述的研究提供了对内分泌细胞功能的新见解,并促进了对包括再生、成熟和糖尿病发病机制等理解不足的过程的高分辨率分子特征分析。这些研究中确定的基因表达程序和途径为发现新的靶点和方法来预防、监测和治疗糖尿病铺平了道路。