Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan.
Diabetes Metab J. 2023 Mar;47(2):173-184. doi: 10.4093/dmj.2022.0324. Epub 2023 Jan 12.
Diabetes is caused by insufficient insulin secretion due to β-cell dysfunction and/or β-cell loss. Therefore, the restoration of functional β-cells by the induction of β-cell differentiation from embryonic stem (ES) and induced-pluripotent stem (iPS) cells, or from somatic non-β-cells, may be a promising curative therapy. To establish an efficient and feasible method for generating functional insulin-producing cells, comprehensive knowledge of pancreas development and β-cell differentiation, including the mechanisms driving cell fate decisions and endocrine cell maturation is crucial. Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have opened a new era in pancreas development and diabetes research, leading to clarification of the detailed transcriptomes of individual insulin-producing cells. Such extensive high-resolution data enables the inference of developmental trajectories during cell transitions and gene regulatory networks. Additionally, advancements in stem cell research have not only enabled their immediate clinical application, but also has made it possible to observe the genetic dynamics of human cell development and maturation in a dish. In this review, we provide an overview of the heterogeneity of islet cells during embryogenesis and differentiation as demonstrated by scRNA-seq studies on the developing and adult pancreata, with implications for the future application of regenerative medicine for diabetes.
糖尿病是由于β细胞功能障碍和/或β细胞丧失导致胰岛素分泌不足引起的。因此，通过诱导胚胎干细胞（ES）和诱导多能干细胞（iPS）细胞或体细胞非β细胞向β细胞分化来恢复功能性β细胞，可能是一种有前途的治疗方法。为了建立一种有效的、可行的方法来产生具有功能的胰岛素分泌细胞，全面了解胰腺发育和β细胞分化的机制，包括驱动细胞命运决定和内分泌细胞成熟的机制至关重要。单细胞 RNA 测序（scRNA-seq）技术的最新进展为胰腺发育和糖尿病研究开辟了一个新时代，阐明了单个胰岛素分泌细胞的详细转录组。这种广泛的高分辨率数据能够推断细胞转换过程中的发育轨迹和基因调控网络。此外，干细胞研究的进展不仅使其能够立即应用于临床，而且还可以在培养皿中观察到人类细胞发育和成熟的遗传动态。在这篇综述中，我们通过对发育中和成年胰腺的 scRNA-seq 研究，概述了胰岛细胞在胚胎发生和分化过程中的异质性，这对再生医学在糖尿病中的未来应用具有重要意义。
