δ-cell conversion to insulin+ bihormonal cells in zebrafish
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA703727 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13759081.fastq.gz | Fastqsanger.gz | |||
| SRR13759082.fastq.gz | Fastqsanger.gz | |||
| SRR13759083.fastq.gz | Fastqsanger.gz | |||
| SRR13759084.fastq.gz | Fastqsanger.gz | |||
| SRR13759085.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 19 |
Similar Datasets
Project description:Restoring damaged b-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study b-cells arising following destruction. We show that most new insulin cells differ from the original b-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to b-cell destruction is fast, efficient and age-independent. Bihormonal cells are transcriptionally close to a subset of d-cells that we identified in control islets and which are characterized by the expression of somatostatin 1.1 (sst1.1) and by genes essential for glucose-induced Insulin secretion in β-cells such as pdx1, slc2a2 and gck. We observed in vivo the conversion of monohormonal sst1.1-expressing cells to sst1.1+ ins+ bihormonal cells following b-cell destruction. Our findings support the conclusion that sst1.1 d-cells possess a pro-b identity enabling them to contribute to the neogenesis of Insulin-producing cells during regeneration. This work unveils that abundant and functional bihormonal cells benefit to diabetes recovery in zebrafish.
2022-01-28 | GSE167187 | GEO
Project description:Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific subtypes of cells, closely related cells with distinct properties. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprogram pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells at the onset of reprogramming in addition to promoting δ-specification. Mafa and Pdx1 suppress δ-specification in α- and β-cell formation. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo.
2013-11-20 | GSE52522 | GEO
Project description:Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific subtypes of cells, closely related cells with distinct properties. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprogram pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells at the onset of reprogramming in addition to promoting δ-specification. Mafa and Pdx1 suppress δ-specification in α- and β-cell formation. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo. induced beta cells samples at day 10 collected for the microarray
2013-11-20 | E-GEOD-52522 | biostudies-arrayexpress
Project description:Introduction: Leptin inhibits insulin secretion from isolated islets from multiple species, but the cell type that mediates this process remains elusive. Several mouse models have been used to explore this question. Ablation of the leptin receptor (Lepr) throughout the pancreatic epithelium results in altered glucose homeostasis and ex vivo insulin secretion and Ca2+ dynamics. However, Lepr removal from neither alpha nor beta cells mimics this result. Moreover, scRNAseq data has revealed an enrichment of LEPR in human islet delta cells. Methods: We confirmed LEPR upregulation in human delta cells by performing RNAseq on fixed, sorted beta and delta cells. We then used a mouse model to test whether delta cells mediate the diminished glucose-stimulated insulin secretion in response to leptin. Results: Ablation of Lepr within mouse delta cells did not change glucose homeostasis or insulin secretion, whether mice were fed a chow or high-fat diet. We further show, using a publicly available scRNAseq dataset, that islet cells expressing Lepr lie within endothelial cell clusters. Conclusions: In mice, leptin does not influence beta-cell function through delta cells.
2023-10-02 | GSE243984 | GEO
Project description:Aiming to identify insulin-independent modulators of glucose homeostasis, we performed a drug screen on zebrafish insulin (ins) mutants and identified androgen receptor (AR) antagonists. To investigate how AR antagonism mediates glucose level reduction in ins mutants, we evaluated the effects of antagonist treatment using transcriptomic studies. RNA-Seq analyses were performed on 120 hours post fertilization (hpf) ins mutants treated with Flutamide or Cyproterone starting at 84 hpf compared to vehicle (DMSO) treated mutants.
2018-12-21 | E-MTAB-7283 | biostudies-arrayexpress
Project description:To discover insulin-independent pathways controlling glucose homeostasis, we generated zebrafish insulin mutants. Aiming to characterize the transcriptional changes induced by deletion of insulin, we performed a microarray analysis comparing insulin mutant animals with their non-mutant siblings at 108 hours post fertilization. Embryos were grown at 28 degrees C until 108 hpf, and were separately collected as mutants or non-mutants to form pools of 10 animals per sample. Total RNA was isolated, sample quality was tested using a Bioanalyzer and microarray analysis was performed by Oak Labs (Germany)
2018-10-20 | E-MTAB-7282 | biostudies-arrayexpress
Project description:Insulin-like 3 affects zebrafish spermatogenic cells directly and via Sertoli cells
| PRJNA638138 | ENA
Project description:Effects of anti-androgenic compounds on zebrafish insulin mutants
| PRJEB30451 | ENA
Project description:Human pancreatic δ cells maintain the balance of pancreatic hormones and loss of δ cells or disruption of somatostatin release is associated with diabetes. Despite their important role, human δ cells are scarce (~5% within the islets), limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. In this study, we established a link between fibroblast growth factor (FGF) signaling pathways and pancreatic δ-cell lineage specification. FGF7 helped maintain a pancreatic endoderm/progenitor state with higher expression levels of PDX1 and CHGA, whereas FGF2 biased cells towards the pancreatic δ-cell lineage by inducing the expression of SST and the δ-cell specific transcription factor HHEX, via FGF receptor 1(FGFR1). We developed a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured b cells and mouse b cells upon transplantation. The generation of somatostatin-secreting pancreatic δ cells from human stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.
2024-06-18 | GSE269764 | GEO
Project description:The islets of Langerhans play a central role in detecting and regulating blood glucose levels. While insulin-producing beta-cells are well-characterized, much remains to be studied about the other cell types in pancreatic islets (alpha-, delta-, PPY-, and epsilon-cells). In this context, we have developed chimeric organoids that we use to understand the interactions between the different cell populations present in pancreatic islets. We previously developed an efficient approach to purify the major cell populations present in pancreatic islets (alpha, beta, and delta) using flow cytometry. We have now developed a technique to re-aggregate these sorted cell populations, enabling the production of clusters (pseudo-islets) in which we can modulate the proportion of each cell population on demand. We generated clusters devoid of delta cells or both alpha and delta cells and confirmed this depletion at the gene and protein levels. We then evaluated the function of these pseudo-islets by measuring glucose-stimulated insulin secretion. The absence of delta-cells did not affect insulin secretion. However, the insulin secretory capacity of pseudo-islets lacking both alpha- and delta-cells was significantly reduced. Transcriptomic analysis of these pseudo-islets did not reveal a loss of beta-cell identity as the cause of the observed functional impairment but highlighted potential new signaling pathways influenced by alpha- and delta-cells. This demonstrates the importance of interactions among different endocrine cell types within the islet for the function of pancreatic beta-cells. It represents a new and effective tool for identifying signaling pathways and compounds that directly or indirectly (via other endocrine cell types) modulate the identity and function of pancreatic endocrine cells.
2025-05-01 | GSE292158 | GEO