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Directed differentiation of pancreatic δ cells from human pluripotent stem cells.
Chen, Lihua; Wang, Nannan; Zhang, Tongran; Zhang, Feng; Zhang, Wei; Meng, Hao; Chen, Jingyi; Liao, Zhiying; Xu, Xiaopeng; Ma, Zhuo; Xu, Tao; Liu, Huisheng.
Afiliación
  • Chen L; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • Wang N; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Zhang T; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Zhang F; College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Zhang W; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Meng H; Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Chen J; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Liao Z; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Xu X; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • Ma Z; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Xu T; Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • Liu H; School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, China.
Nat Commun ; 15(1): 6344, 2024 Jul 27.
Article en En | MEDLINE | ID: mdl-39068220
ABSTRACT
Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured ß cells and mouse ß cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Madre Pluripotentes Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Células Madre Pluripotentes Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido