Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258195 | ENA |
REPOSITORIES: ENA
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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 | GSE185035 | 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:Objectives: 1. To explore cell population changes after a 4-week in vitro self-reaggregation culture, comparing RMF pellets, native fat tissue, and expanded ADSCs. 2. To analysis the cellular composition and maturity of RMF-islet organoids before and post transplantation. Methods: Sc-Seq was performed on cells from RMF pellets (n = 3), native fat (n = 3), expanded ADSCs (n = 3), in vitro RMF-islet organoids (n = 2), and in vivo RMF-islet organoid grafts (n = 2) using the 10× Genomics platform. Results: A total of 65501 cells were clustered from the RMF pellets, native fat, and expanded ADSC samples and visualized using UMAP. Cells were categorized into main cell types based on their spatial distribution on the UMAP plots: adipose-derived stem and progenitor cell (ASPC) clusters (ASPC-1, ASPC-2, ASPC-3, and ASPC-4), preadipocyte cluster, endothelial cell cluster, smooth muscle cell cluster (SMC), and immune cell cluster. Following a 4-week in vitro culture, the percentage of ASPCs increased from 24.57% in native fat to 97.17% in RMF pellets and further to 99.9% in expanded ADSCs. Pseudotime analyses the ASPC-1 cluster, predominantly derived from native fat samples (96.04%), occupied the initial position on the developmental trajectory, followed by ASPC-2 and ASPC-3 clusters primarily originating from RMF pellet samples (94.91% and 96.55%, respectively). Conversely, the ASPC-4 cluster mainly derived from expanded ADSC samples were positioned at the terminal end of the trajectory. Furthermore, pseudotime values indicated that both ASPC-2 and ASPC-3 clusters from RMF pellet samples exhibited an intermediate differentiation state between those observed in native fat and expanded ADSC samples. For RMF-islet organoids, a total of 8715 cells and 5328 cells were analyzied from the in vitro and in vivo RMF-islet organoid samples, respectively. Compared these data with published transcriptomes of human islet cells, we identified four distinct populations of pancreatic endocrine cells, including β-, α-, δ-, or γ-like cells, within the two in vitro RMF-islet organoid samples and the presence of all four major pancreatic endocrine cell types within the organoid grafts and displayed a similar cellular composition before and after transplantation. Conclusion: 1. ASPC clusters from RMF pellet samples possess an intermediary differentiated phenotype compared to their counterparts derived from native fat and expanded ADSC samples. 2. The RMF-islet organoids harbor a population of functionally matured β-like cells exhibiting transcriptional similarities to native human islet β-cells.
2025-10-28 | GSE280107 | 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:Using quantitative phosphoproteomic analysis of human islets and human stem-cell-derived islets (SC-islets), we show that mTORC1 inhibition with Torin-1 or rapamycin induces significant alterations in the phosphorylation profile of human islet cells.
2025-05-12 | PXD062389 | Pride
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
Project description:<p>Background</p><p>Omega-3 polyunsaturated fatty acids (PUFAs) are known to protect against type 1 diabetes mellitus (T1DM), but how they act through the gut-islet axis is not fully understood. This study explored how Omega-3 PUFA-influenced gut microbiota and their metabolites help protect pancreatic islets in T1DM.</p><p>Methods</p><p>We used fecal microbiota transplantation (FMT) to test the effects of Omega-3 PUFA-derived gut microbiota in NOD mice. Immune cell changes in the islets were analyzed using transcriptomics, flow cytometry, and immunohistochemistry. Metabolomics identified key metabolites in serum related to gut microbiota changes. Co-culture experiments examined the role of specific metabolites in macrophage polarization and β-cell function.</p><p>Results</p><p>Omega-3 PUFA-treated and FMT mice showed reduced islet inflammation and an increased abundance of the Eubacterium coprostanoligenes group. Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) was strongly linked to E. coprostanoligenes and stood out as a key molecule. In co-culture experiments, 18β-GA shifted macrophages to an M2 phenotype, which boosted insulin production and secretion in β-cells.</p><p>Conclusions</p><p>Omega-3 PUFA-derived gut microbiota and the metabolite 18β-GA play a key role in protecting pancreatic islets in T1DM by modulating macrophage polarization and improving β-cell function. These findings suggest new ways to use gut microbiota for T1DM treatment.</p>
2026-06-13 | MTBLS13979 | MetaboLights
Project description:<p>Background</p><p>Omega-3 polyunsaturated fatty acids (PUFAs) are known to protect against type 1 diabetes mellitus (T1DM), but how they act through the gut-islet axis is not fully understood. This study explored how Omega-3 PUFA-influenced gut microbiota and their metabolites help protect pancreatic islets in T1DM.</p><p>Methods</p><p>We used fecal microbiota transplantation (FMT) to test the effects of Omega-3 PUFA-derived gut microbiota in NOD mice. Immune cell changes in the islets were analyzed using transcriptomics, flow cytometry, and immunohistochemistry. Metabolomics identified key metabolites in serum related to gut microbiota changes. Co-culture experiments examined the role of specific metabolites in macrophage polarization and β-cell function.</p><p>Results</p><p>Omega-3 PUFA-treated and FMT mice showed reduced islet inflammation and an increased abundance of the Eubacterium coprostanoligenes group. Enhanced M2 macrophage polarization was observed in the islet microenvironment of FMT mice. Among gut microbiota metabolites, 18β-glycyrrhetinic acid (18β-GA) was strongly linked to E. coprostanoligenes and stood out as a key molecule. In co-culture experiments, 18β-GA shifted macrophages to an M2 phenotype, which boosted insulin production and secretion in β-cells.</p><p>Conclusions</p><p>Omega-3 PUFA-derived gut microbiota and the metabolite 18β-GA play a key role in protecting pancreatic islets in T1DM by modulating macrophage polarization and improving β-cell function. These findings suggest new ways to use gut microbiota for T1DM treatment.</p>
2026-06-13 | MTBLS13174 | MetaboLights
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