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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [human_singlecell]

ABSTRACT: Pluripotent stem cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment. Here, we demonstrate that transplantation of pluripotent stem cell-derived islets into diabetic nonprimates effectively restored endogenous insulin secretion and improved glycemic control. Single-cell RNA sequencing analysis of S6D2 clusters confirmed the existence of the three major pancreatic endocrine cell populations (β cells, α-like cells and δ-like cells) and their proportions, which altogether accounted for 80%. Importantly, hierarchical clustering of S6D2 hCiPSC-islets, 10 wpt kidney grafts and primary islets showed that the hCiPSC differentiated pancreatic endocrine cells shared similar global gene expression profiles to their native counterparts in primary islets. Single-cell RNA sequencing analysis on PBMCs revealed the potential immune response of recipient macaque to hCiPSC-islets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE185036 | GEO | 2022/02/04

REPOSITORIES: GEO

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [monkey_singlecell]

Project description:Human pluripotent stem cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment. Here, we demonstrate that transplantation of human pluripotent stem cell-derived islets into diabetic nonhuman primates effectively restored endogenous insulin secretion and improved glycemic control. Single-cell RNA sequencing analysis of S6D2 clusters confirmed the existence of the three major pancreatic endocrine cell populations (β cells, α-like cells and δ-like cells) and their proportions, which altogether accounted for 80%. Importantly, hierarchical clustering of S6D2 hCiPSC-islets, 10 wpt kidney grafts and primary human islets showed that the hCiPSC differentiated pancreatic endocrine cells shared similar global gene expression profiles to their native counterparts in primary human islets. Single-cell RNA sequencing analysis on PBMCs revealed the potential immune response of recipient macaque to hCiPSC-islets.

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [human_bulk]

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates

Project description:Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [human_singlecell]

Project description:Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [human_singlecell]

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Project description:Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [monkey_singlecell]

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates [human_bulk]

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Human Pluripotent Stem Cell-derived Islets Ameliorate Diabetes in Nonhuman Primates

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-04 | GSE185038 | GEO

Age-associated DNA methylation increases in mouse pancreatic islets suggest an epigenetic drift toward the exocrine pancreas epigenome

Project description:Early postnatal overnutrition causes persistent dysregulation of endocrine pancreas function. We used genome-scale DNA methylation profiling in the suckling-period small litter (SL) mouse model to test whether this occurs via persistent epigenetic changes in pancreatic islets. Although SL islets showed DNA methylation changes directly after weaning and in adulthood, few of these were present at both ages, contrary to our hypothesis. Most interestingly, we discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging. Focusing on a subset of genes relevant to β cell function, we showed that these methylation differences are strongly correlated with expression. Together, our results provide the novel insight that DNA methylation changes that occur as islets age indicate an overall epigenetic drift toward the exocrine pancreas epigenome. These concerted shifts in the islet methylome could contribute to the age-associated decline in endocrine pancreas function. Pancreatic islets were isolated from P21/P180 SL or C mice. To ensure purity of islets, 3 rounds of manual picking were performed in each samples. Whole pancreas samples, ~98% of which is exocrine pancreas, were used as exocrine pancreas. There are 5 mice per group.

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