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Islet organoid as a promising model for diabetes

Protein & cell 2022年第4期13卷 239-257页

作者： Xiaofei Zhang Zhuo Ma Eli Song Tao Xu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangzhou Regenerative Medicine and Health Guangdong Laboratory(Bioland Laboratory) Guangzhou 510005China

Studies on diabetes have long been hampered by a lack of authentic disease models that,ideally,should be unlimited and able to recapitulate the abnormalities involved in the development,structure,and function of human pancreatic islets under pathological *** cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native ***,islet organoids hold great promise for modeling islet development and function,deciphering the mechanisms underlying the onset of diabetes,providing an in vitro human organ model for infection of viruses such as SARS-CoV-2,and contributing to drug screening and autologous islet ***,the currently established islet organoids are generally immature compared with native islets,and further efforts should be made to improve the heterogeneity and functionality of islet organoids,making it an authentic and informative disease model for ***,we review the advances and challenges in the generation of islet organoids,focusing on human pluripotent stem cell-derived islet organoids,and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.

关键词： islet organoid diabetes pluripotent/adult stem cell pancreaticβcell disease model

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Single-cell RNA Sequencing Reveals Sexually Dimorphic Transcriptome and Type 2 Diabetes Genes in Mouse Islet β cells

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Genomics, Proteomics & Bioinformatics 2021年第3期19卷 408-422页

作者： Gang Liu Yana Li Tengjiao Zhang Mushan Li Sheng Li Qing He Shuxin Liu Minglu Xu Tinghui Xiao Zhen Shao Weiyang Shi Weida Li Translational Medical Center for Stem cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Tsingtao Advanced Research Institute Tongji UniversityQingdao 266073China CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China Department of Statistics The Pennsylvania State UniversityUniversity ParkPA 16802USA Ministry of Education Key Laboratory of Marine Genetics and Breeding College of Marine Life SciencesOcean University of ChinaQingdao 266003China

Type 2 diabetes(T2D)is characterized by the malfunction of pancreaticβ*** and pathogenesis of T2D can be affected by multiple factors,including sex ***,the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain *** single-cell RNA sequencing(scRNA-seq),we demonstrate the presence of sexually dimorphic transcriptomes in mouseβ*** a high-fat diet-induced T2D mouse model,we identified sex-dependent T2D altered genes,suggesting sex-based differences in the pathological mechanisms of ***,based on islet transplantation experiments,we found that compared to mice with sexmatched islet transplants,sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway ofβ***,the diabetic mice with sex-mismatched islet transplants showed impaired glucose *** data suggest sexual dimorphism in T2D pathogenicity,indicating that sex should be considered when treating *** hope that our findings could provide new insights for the development of precision medicine in T2D.

关键词： Type 2 diabetes mellitus pancreaticβcell Sex-biased gene expression Sex-dependent T2D altered genes Precision medicine

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Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells

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cell Regeneration 2022年第1期11卷 227-245页

作者： Wenwen Jin Wei Jiang Department of Biological Repositories Frontier Science Center for Immunology and MetabolismMedical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan 430071China Human Genetics Resource Preservation Center of Wuhan University Wuhan 430071China

pancreaticβcells differentiated from stem cells provide promise for cell replacement therapy of *** pluripotent stem cells could be differentiated into definitive endoderm,followed by pancreatic progenitors,and then subjected to endocrinal differentiation and maturation in a stepwise *** achievements have been made in making pancreaticβcells from human pluripotent stem cells in last two decades,and a couple of phase I/II clinical trials have just been ***,we overview the major progresses in differentiating pancreaticβcells from human pluripotent stem cells with the focus on recent technical advances in each differentiation stage,and briefly discuss the current limitations as well.

关键词： pancreaticβcell Human pluripotent stem cells Stepwise differentiation Diabetes mellitus

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