Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparative single-cell transcriptomic analysis of human primary and stem cell-derived islets under acute hypoxia

ABSTRACT: To understand the divergent responses of different islet sources to the hypoxic stress encountered post-transplantation, we performed a direct, comparative single-cell RNA sequencing analysis of human primary islets and stem cell-derived islets (SC-islets, HUES8 line) over an acute time course (0, 6, 24, and 48 hours) of hypoxic exposure (1% O2). Our data reveal that while both islet types activate conserved core stress pathways, they subsequently execute markedly divergent adaptive strategies. Primary β-cells navigate hypoxia through a profound suppression of their mature identity and a shift towards a quiescent, energy-conserving state. In contrast, SC-β cells mount a highly plastic and metabolically dynamic response that is coupled with significant lineage instability and functional dysregulation. These findings highlight fundamental, source-specific differences in hypoxic adaptation, providing a rich resource for developing tailored strategies to improve islet transplantation success.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301598 | GEO | 2026/04/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CRISPR Screening to Investigate Stem Cell-Derived Islets

Project description:Genetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy. However, genetic perturbations for improving transplantation efficacy have yet to be elucidated. To identify potential targets, we performed an unbiased whole-genome CRISPR-activation screen in transplanted stem cell-derived islets (SC-islets). We first created a stem cell line with CRISPR-activation components (HUES8-VPR). We transduced the HUES8-VPR stem cells with a lentiviral guide RNA library targeting the whole human genome. These transduced stem cells were differentiated into SC-islets, transplanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice, and then extracted for next-generation sequencing. The screen identified multiple candidates, including the Fc alpha/mu receptor (FCAMR). In vitro characterization revealed that FCAMR overexpression did not negatively affect SC-islet function or transcriptomic identity. Mice transplanted with SC-islets overexpressing FCAMR had increased blood glucose levels and increased cpeptide compared to controls. Furthermore, mice receiving FCAMR-modified grafts maintained a higher body weight compared to controls in a diabetic setting. Our study utilizes a screening approach to identify potential candidates for improving SC-islet therapies.

2026-05-20 | GSE305932 | GEO

Improve cellular fitness of human stem cell-derived islets under hypoxia

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

Generation of functional human pancreatic beta cells in vitro

Project description:The generation of insulin-producing pancreatic cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes. However, insulin-producing cells previously generated from human pluripotent stem cells (hPSC) lack many functional characteristics of bona fide β cells. Here we report a scalable differentiation protocol that can generate hundreds of millions of glucose-responsive β cells from hPSC in vitro. These stem cell derived cells (SC) express markers found in mature β cells, flux Ca2+ in response to glucose, package insulin into secretory granules and secrete quantities of insulin comparable to adult β cells in response to multiple sequential glucose challenges in vitro. Furthermore, these cells secrete human insulin into the serum of mice shortly after transplantation in a glucose-regulated manner, and transplantation of these cells ameliorates hyperglycemia in diabetic mice. Differentiated cells were sorted and processed for RNA isolation using the MARIS protocol published previously (PMID: 24516164.) Human embryonic stem cell (hESC) line HUES8 was differentiated into SC-beta cells. Two biological replicates were analyzed. Those data were normalized together with and compared to existing, previously published data from Hrvatin et al. ( (PMID: 24516164) from human islet -derived insulin+ cells, undifferentiated HUES8 hES cells, and insulin+ cells derived from HUES8 cells according to previously published protocols.

2014-09-25 | E-GEOD-61714 | biostudies-arrayexpress

Single nuclei multiomics of human stem cell-derived islets identifies deficiencies in lineage specification

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

RNA Seq of IAPP expressing SC-β cells

Project description:Islet transplantation for treatment of diabetes is limited by availability of donor islets and requirements for immunosuppression. Stem cell-derived islets might circumvent these issues. SC-islets effectively control glucose metabolism post transplantation, but do not yet achieve full function in vitro with currently published differentiation protocols. We aimed to identify markers of mature subpopulations of SC-β cells by studying transcriptional changes associated with in vivo maturation of SC-β cells using RNA-seq and co-expression network analysis. The β cell-specific hormone islet amyloid polypeptide (IAPP) emerged as the top candidate to be such a marker. IAPP+ cells had more mature β cell gene expression and higher cellular insulin content than IAPP- cells in vitro. IAPP+ INS+ cells were more stable in long-term culture than IAPP- INS+ cells and retained insulin expression after transplantation into mice. Finally, we conducted a small molecule screen to identify compounds that enhance IAPP expression. Aconitine up-regulated IAPP and could help to optimize differentiation protocols.

2024-04-15 | GSE263366 | GEO

Pre-adaptation of Stem Cell-Derived Islet Organoids to Hypoxia via Zinc Transportation Inhibition Drives Rapid Neo-vascularization

Project description:Human stem cell-derived islet organoids (SC-islets) hold great potential for diabetes treatment, but their clinical application is hindered by immaturity and ischemia-induced dysfunction post transplantation. Hypoxia-driven angiogenesis via the HIF1A-VEGFA axis is a common adaptation, but the metabolic fragility of SC-islet β cell leads to early functional damage and suppressed VEGFA release, thereby delaying vascularization and causing graft loss. The key challenge in SC-islet transplantation is how to prevent hypoxia-induced stress and promote rapid neo-vascularization. To reconcile this discrepancy, we targeted zinc transportation using a chemical inhibitor to enhance SC-islet maturation, hypoxia resistance and vascularization. We found that excessive zinc in SC-islet β-cells induces oxidative modification that inhibits AMPK activity. Chemical inhibition of zinc transportation activates AMPK, simultaneously enhances functional maturation, improves hypoxia resistance and increases VEGFA expression to facilitate endothelial cell integration. In diabetic animal models, this approach significantly improved hypoxia resistance, accelerated neo-vascularization, and enhanced glycemic control. Our findings demonstrate that chemical inhibition of zinc transportation boosts SC-islet functional competence, offering a potential strategy to advance the paradigm of functional pre-adaptation to stress in regenerative medicine.

2026-02-10 | GSE293322 | GEO

Engineered vasculature induces functional maturation of pluripotent stem cell-derived islet organoids

Project description:Blood vessels play a critical role in pancreatic islet function, yet current methods for deriving islet organoids from human pluripotent stem cells (SC-islets) lack vasculature. We engineered 3D vascularized SC-islet organoids by assembling SC-islet cells, human primary endothelial cells (ECs) and fibroblasts in a non-perfused model and a microfluidic device with perfused vessels. Vasculature improved stimulus-dependent Ca2+ influx into SC-β-cells, a hallmark of β-cell function that is blunted in non-vascularized SC-islets. Furthermore, vascularization accelerated diabetes reversal post-engraftment of a subtherapeutic SC-islet dose. We show that vasculature leads to formation of an islet-like basement membrane that contributes to functional improvement of SC-β-cells. Furthermore, scRNA-seq data predicted BMP2/4-BMPR2 signaling from ECs to SC-β cells, and correspondingly, BMP4 enhanced the SC-β cell Ca2+ response and insulin secretion. Vascularized SC-islets will enable further studies of crosstalk between β-cells and ECs and will serve as an in vitro platform for disease modeling and therapeutic testing.

2025-08-20 | GSE276815 | GEO

Human pancreas and SC-beta phosphoproteomics

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

Controlling human stem cell-derived islet composition using magnetic sorting

Project description:Stem cell-derived islets (SC-islets) hold significant promise for treating diabetes, but optimizing their functional maturity remains a challenge. CD49a, an integrin subunit involved in cell adhesion and signaling, has been identified as a potential marker associated with islet cell differentiation. In this study, we employed magnetic-activated cell sorting (MACS) to isolate CD49a-enriched and CD49a-depleted populations from SC-islets. These two distinct populations were evaluated for functional and molecular differences using single-cell RNA sequencing (scRNA-seq), in vitro glucose-stimulated insulin secretion (GSIS), and in vivo transplantation. Our scRNA-seq analysis revealed distinct transcriptional profiles between the CD49a-enriched and CD49a-depleted populations, with the CD49a-enriched population exhibiting higher expression of key β cell lineage markers, including insulin. Functional assays demonstrated that CD49a-enriched SC-islets had significantly improved GSIS, indicative of enhanced β cell functionality. Additionally, when transplanted into mice, the CD49a-enriched SC-islets exhibited superior graft performance, as evidenced by human C-peptide secretion. These findings support that CD49a enrichment through MACS represents a promising approach to enhance the functional maturity of SC-islets. Further investigations into the role of CD49a in islet cell differentiation and function may facilitate the development of more effective stem cell-based therapies for diabetes.

2025-01-28 | GSE278800 | GEO

Transcription profiling by array of human pacreatic islets prepared for clinical transplantation

Project description:This study compared 9 human islet preparations, extracted and prepared for clinical transplantation. Human islets were isolated as, and all were of transplant quality. Unamplified RNA was extracted and hybridized to Affymetrix HGU133+2 arrays. By using gene set enrichment analysis to investigate the variability of each probeset on the array, it was clear that isolated human islets undergo varying degrees of hypoxic stress. Further to this, key glycolytic genes, all of which are under the control of hypoxia inducing factor 1a (HIF-1a) were activated, indicating a switch towards anareobic glycolysis. Glycolysis severely impairs the ability of islets to sense glucose and secrete insulin in response to elevated blood sugar. We confirmed these findings in mouse rodents, demonstrated a dependance upon HIF-1a, and showed that even after 4 weeks, hypoxic islets retained their glycolytic molecular profile.

2011-02-26 | E-MTAB-203 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data