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 | 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: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:Stem cell-derived islet (SC-islet) cell therapy holds immense potential for the treatment of Type 1 Diabetes. However, low oxygen supply leads to cell dysfunction post-transplantation, especially in subcutaneous spaces and encapsulation devices. The response of SC-islets to hypoxia and effective strategies to alleviate its detrimental effects remain poorly understood. This study investigates the impact of hypoxia on SC-islets and elucidate the dynamics of hypoxia-induced stress. We performed transcriptional profiling of human SC-islets exposed to hypoxic conditions, and drew the transcriptomic and epigenetic profiles of single cells. Our findings demonstrate that β cells within SC-islets gradually undergo a decline in cell identity and metabolic function in response to hypoxia. The loss of expression from immediate early genes, specifically EGR1, FOS, and JUN, results in the downregulation of key transcription factors (TFs) that are essential for maintaining SC-islet cell identity under hypoxic conditions. By comparing SC-islets under low and high oxygen conditions, we identified genes that play a role in maintaining the fitness of SC-islets in a low-oxygen environment. Notably, the expression of EDN3, a potent vasoconstrictor gene that is enriched in native pancreatic β cells, significantly aids in preserving β cell identity under hypoxic conditions. Elevated expression of EDN3 in SC-islets effectively mitigated the deleterious effects of hypoxia by modulating genes involved in SC-islet maturation including genes associated with glucose sensing and regulation in β cells. These insights improve the understanding of SC-islets under hypoxic conditions, offering a potential point of intervention for future clinical applications in the treatment of Type 1 Diabetes
2025-03-24 | GSE263130 | GEO
Project description:Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and from primary childhood and adult pancreas for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a previously unrecognized, transient CDX2-expressing β-cell-related population in fetal pancreas, arguing against a non-pancreatic origin as proposed. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro β-cell maturation and identify sex hormones as drivers of childhood β-cell proliferation. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem cell-derived islets and a framework for manipulating cell identities and maturity.
2023-03-02 | GSE202492 | GEO