Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258195 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2022-02-04 | GSE185036 | GEO
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.
2022-02-04 | GSE185037 | GEO
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.
2022-02-04 | GSE185035 | GEO
Project description:We profiled the transcritpome and ATAC profiles of human pancreatic islets generated from pluripotent stem cells. Multiomic profiling was also performed on primary human islets and in vivo matured SC-islets for comparision. We catalogued the ATAC associated signatures for each cell types in SC-islets and compared them to their human primiary islet counterparts. In vivo maturation of SC-islets were also compared with in vitro SC-islets. In this study, we identified key regulators associated with islet identity during differentiation and maturation. Gene manipulation of CTCF affects differentiating SC-islet cell fate to enteroendocrine-like lineage. ARID1B knockdown caueses islet cells to present mature signatures. These gene altered SC-islets were also sequenced.
2023-03-25 | GSE199636 | GEO
Project description:Human pancreatic islets were isolated from pancreas of deceased donors by Ricordi's procedure and cultured in CMRL 1066 medium additioned with human albumin. EVs were isolated from conditioned medium derived from islet culture after isolation. Once isolated, RNA of islets and islet-derived EVs was extracted and analyzed for microRNA expression within 48 hours after isolation.
2012-07-30 | E-MEXP-3691 | biostudies-arrayexpress
Project description:Stem cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human stem cells differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment, and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, stem cell-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, stem cell-derived tissues are amenable to functional improvement by circadian modulation.
2019-11-16 | GSE140500 | GEO
Project description:Stem cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human stem cells differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment, and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, stem cell-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, stem cell-derived tissues are amenable to functional improvement by circadian modulation.
2019-11-02 | GSE139816 | GEO
Project description:Stem cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human stem cells differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment, and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, stem cell-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, stem cell-derived tissues are amenable to functional improvement by circadian modulation.
2019-11-16 | GSE140501 | GEO
Project description:Stem cell-derived tissues could transform disease research and therapy, yet most methods generate functionally immature products. We investigate how human stem cells differentiate into pancreatic islets in vitro by profiling DNA methylation, chromatin accessibility, and histone modification changes. We find that enhancer potential is reset upon lineage commitment, and show how pervasive epigenetic priming steers endocrine cell fates. Modeling islet differentiation and maturation regulatory circuits reveals genes critical for generating endocrine cells and identifies circadian control as limiting for in vitro islet function. Entrainment to circadian feeding/fasting cycles triggers islet metabolic maturation by inducing cyclic synthesis of energy metabolism and insulin secretion effectors, including antiphasic insulin and glucagon pulses. Following entrainment, stem cell-derived islets gain persistent chromatin changes and rhythmic insulin responses with a raised glucose threshold, a hallmark of functional maturity, and function within days of transplantation. Thus, stem cell-derived tissues are amenable to functional improvement by circadian modulation.
2019-11-16 | GSE140499 | GEO
Project description:Pancreatic islet transplantation as a cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols, and their potential for differentiation into functional beta cells, remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and attempted re-differentiation. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at re-differentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increases our understanding of the active pathways in expanded and re-differentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta cell mass in T1D patients. Experiment Overall Design: In this study, we have tested three different protocols to expand human pancreatic islets in monolayer and after attempted maneuvers to re-differentiate the expanded cells back to islets. We have characterized the resulting cells in detail by performing microarray analyses with fresh pancreatic islets, expanded islet cells and re-differentiated cells. Genes modified by either of three protocols have 70 to 80% overlap with the genes changed by the other two protocols. Although there are promising changes in the right direction, none of the three protocols could achieve a return to a functional islet state. The expanded cells highly resemble Mesenchymal Stem Cells (MSC), and similar gene regulatory networks seem to be active in both cell types. On the other hand, the expanded islet cells are different from MSC in that they seem to retain activity of some islet gene modules. The current results highlight the importance of designing new strategies that take into account the MSC potential of expanded cells.
2009-08-07 | E-GEOD-15543 | biostudies-arrayexpress