Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
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干细胞来源的人胰岛的功能、代谢和转录成熟。
DOI：
10.1038/s41587-022-01219-z
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发表时间：
2022-07
影响因子：
46.9
通讯作者：
Otonkoski, Timo
中科院分区：
文献类型：
--
作者：
Balboa, Diego;Barsby, Tom;Lithovius, Vaino;Saarimaki-Vire, Jonna;Omar-Hmeadi, Muhmmad;Dyachok, Oleg;Montaser, Hossam;Lund, Per-Eric;Yang, Mingyu;Ibrahim, Hazem;Naatanen, Anna;Chandra, Vikash;Vihinen, Helena;Jokitalo, Eija;Kvist, Jouni;Ustinov, Jarkko;Nieminen, Anni I.;Kuuluvainen, Emilia;Hietakangas, Ville;Katajisto, Pekka;Lau, Joey;Carlsson, Per-Ola;Barg, Sebastian;Tengholm, Anders;Otonkoski, Timo
人多能干细胞来源的胰岛细胞移植是治疗糖尿病的一种有前景的方法。尽管在干细胞衍生的胰岛（SC-胰岛）的生成方面取得了进展，但尚未对其功能特性进行详细表征。在这里，我们使用优化的方案生成功能成熟的SC胰岛，并将其与原代成人胰岛进行全面的基准测试。双相葡萄糖刺激的胰岛素分泌在体外成熟过程中发展，与细胞结构重组和α细胞的存在增加有关。SC-胰岛的电生理、信号传导和胞吐作用与成人胰岛相似。尽管糖酵解和线粒体葡萄糖代谢存在差异，但仍实现了葡萄糖响应性胰岛素分泌。SC-胰岛的体外单细胞转录组学和在小鼠中植入的整个6个月揭示了一个连续的成熟轨迹，最终在转录景观非常相似的初级胰岛。我们对SC-胰岛成熟的全面评估突出了它们的高级功能，并支持它们在进一步了解和防治糖尿病方面的应用。来源于干细胞的胰岛以原代细胞为基准。
Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes. Pancreatic islets derived from stem cells are benchmarked against primary cells.
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影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
8.8
作者：
Davis, Jeffrey C.;Alves, Tiago C.;Melton, Douglas A.
通讯作者：
Melton, Douglas A.
影响因子：
7.7
作者：
Balboa D;Saarimäki-Vire J;Borshagovski D;Survila M;Lindholm P;Galli E;Eurola S;Ustinov J;Grym H;Huopio H;Partanen J;Wartiovaara K;Otonkoski T
通讯作者：
Otonkoski T
影响因子：
8.1
作者：
Benazra, Marion;Lecomte, Marie-Jose;Ravassard, Philippe
通讯作者：
Ravassard, Philippe
影响因子：
7.7
作者：
Henquin, Jean-Claude;Dufrane, Denis;Nenquin, Myriam
通讯作者：
Nenquin, Myriam