Drosophila adult insulin producing cell transcriptome
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB50165 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We aimed to assess whether Wnt-modulation could contribute to mature hiPSC-derived insulin-producing cells in vitro. Building our hypothesis on our previous findings of Wnt activation in immature hiPSC-derived insulin-producing cells compared to adult human islets and with recent data reporting a link between Wnt/PCP and in vitro beta-cell maturation. In this study we stimulated hiPSC-derived insulin-producing cells with syntetic proteins including WNT3A, WNT4, WNT5A and WNT5B as well as inhibiting endogeneous Wnt signaling with Tankyrase inhibitor G007-LK.
2019-11-13 | PXD012081 | Pride
Project description:Transgenerational epigenetic inheritance is a subject of immense current interest. In a newly developed Drosophila model in the laboratory, genetic ablation of insulin-producing cells (IPCs) was found to affect whole -body triglyceride levels not only in the ablated flies but also in their male-line derived, non-ablated future generations. To further characterize this genetic-factor-induced transgenerational inheritance model, we have now performed whole body microarray gene expression profiling of adult males and females with genetically ablated IPCs, and of three consecutive, paternally derived non-ablated generations of adult males and females originating from ablated males. Interestingly, like altered levels of triglycerides, transcriptomic alterations are found not only in the ablated flies but also in their male-line-derived, non-ablated future generations.
2023-04-21 | GSE184339 | GEO
Project description:A Drosophila microRNA (dme-miR-14) is involved in regulating the levels of insulin-like peptides (ilps) from the neuronal insulin-producing cells (IPCs). This is crucial for regulation of fat content in adult flies. Finding the target of this microRNA is crucial for understanding the regulation of ilp gene expression. We used microarrays to identify genes that are upregulated specifically in the neuronal IPCs in the microRNA mutants.
2011-02-01 | GSE20202 | GEO
Project description:A Drosophila microRNA (dme-miR-14) is involved in regulating the levels of insulin-like peptides (ilps) from the neuronal insulin-producing cells (IPCs). This is crucial for regulation of fat content in adult flies. Finding the target of this microRNA is crucial for understanding the regulation of ilp gene expression. We used microarrays to identify genes that are upregulated specifically in the neuronal IPCs in the microRNA mutants. Drosophila adult head RNA was extracted and hybridized on Affymetrix microarrays. We reared animals from early larval stages in controlled growth and feeding conditions. RNA was extracted from 5-day-old adult males. We collected RNA from control, homozygous dme-miR-14 mutants and mutants expressing dme-miR-14 microRNA specifically in the IPCs (rescue). We were interested in genes that were upregulated in the mutants and were restored or reduced to control levels in the rescue condition. Two biological replicates per sample type were performed.
2011-02-01 | E-GEOD-20202 | biostudies-arrayexpress
Project description:Insulin and IGF signaling (IIS) is a complex system that controls diverse processes including growth, development, metabolism, stress responses and aging. Drosophila melanogaster IIS is propagated by eight Drosophila insulin-like peptides (DILPs), homologues of both mammalian insulin and IGFs, with various spatiotemporal expression patterns and functions. DILPs 1-7 are thought to act through a single Drosophila insulin/IGF receptor, InR, but it is unclear how the DILPs thereby mediate a range of physiological phenotypes. We determined the distinct cell signaling effects of DILP2 and DILP5 stimulation upon Drosophila S2 cells. DILP2 and DILP5 induced similar transcriptional patterns, but differed in signal transduction kinetics. DILP5 induced sustained phosphorylation of Akt, while DILP2 produced acute, transient Akt phosphorylation. Accordingly, we used phosphoproteomic analysis to identify distinct patterns of non-genomic signaling induced by DILP2 and DILP5. Across all treatments and replicates, 5250 unique phosphopeptides were identified, representing 1575 proteins. Among these peptides, DILP2, but not DILP5, dephosphorylated Ser15 on glycogen phosphorylase (GlyP), and DILP2, but not DILP5, was subsequently shown to repress enzymatic GlyP activity in S2 cells. The functional consequences of this difference were evaluated in adult Drosophila dilp mutants: dilp2 null adults have elevated GlyP enzymatic activity relative to wildtype, while dilp5 mutants have reduced GlyP activity.
2018-10-19 | PXD009240 | Pride
Project description:β cell proliferation rates decline with age and adult β cells have limited self-duplicating activity for regeneration, which predisposes to diabetes. Here we show that, among MYC family members, Mycl was expressed preferentially in proliferating immature endocrine cells. Genetic ablation of Mycl caused a modest reduction in cell proliferation of pancreatic endocrine cells in neonatal mice. By contrast, systemic expression of Mycl in mice stimulated proliferation in pancreatic islet cells and resulted in expansion of pancreatic islets without forming tumors in other organs. Single-cell RNA sequencing and genetic tracing experiments revealed that the expression of Mycl provoked transcription signatures associated with immature proliferating endocrine cells and stimulated self-duplication in adult hormone-expressing cells. The expanded hormone-expressing cells ceased proliferation but persisted after withdrawal of Mycl expression. Remarkably, a subset of the expanded α cells gave rise to insulin-producing cells after the withdrawal. Moreover, transient Mycl expression in vivo was sufficient to normalize increased blood glucose levels in diabetic mice evoked by chemical ablation of β cells. In vitro expression of Mycl similarly provoked active replication without inducing apoptosis in adult hormone-expressing islet cells, even those from aged mice. Furthermore, the expanded islet cells functioned in diabetic mice after transplantation. Finally, we show that MYCL stimulated self-duplication of human adult cadaveric islet cells. Collectively, these results demonstrate that sole induction of Mycl expands adult β cells both in vivo and in vitro. Moreover, islet cell-specific reprogramming via transient Mycl transduction elicits endogenous expansion of insulin-producing cells in adult pancreas through both self-duplication of β cells and transdifferentiation ofα cells into insulin-producing cells, which may provide a regenerative strategy of β cells.
2022-01-29 | GSE163947 | GEO
Project description:β cell proliferation rates decline with age and adult β cells have limited self-duplicating activity for regeneration, which predisposes to diabetes. Here we show that, among MYC family members, Mycl was expressed preferentially in proliferating immature endocrine cells. Genetic ablation of Mycl caused a modest reduction in cell proliferation of pancreatic endocrine cells in neonatal mice. By contrast, systemic expression of Mycl in mice stimulated proliferation in pancreatic islet cells and resulted in expansion of pancreatic islets without forming tumors in other organs. Single-cell RNA sequencing and genetic tracing experiments revealed that the expression of Mycl provoked transcription signatures associated with immature proliferating endocrine cells and stimulated self-duplication in adult hormone-expressing cells. The expanded hormone-expressing cells ceased proliferation but persisted after withdrawal of Mycl expression. Remarkably, a subset of the expanded α cells gave rise to insulin-producing cells after the withdrawal. Moreover, transient Mycl expression in vivo was sufficient to normalize increased blood glucose levels in diabetic mice evoked by chemical ablation of β cells. In vitro expression of Mycl similarly provoked active replication without inducing apoptosis in adult hormone-expressing islet cells, even those from aged mice. Furthermore, the expanded islet cells functioned in diabetic mice after transplantation. Finally, we show that MYCL stimulated self-duplication of human adult cadaveric islet cells. Collectively, these results demonstrate that sole induction of Mycl expands adult β cells both in vivo and in vitro. Moreover, islet cell-specific reprogramming via transient Mycl transduction elicits endogenous expansion of insulin-producing cells in adult pancreas through both self-duplication of β cells and transdifferentiation ofα cells into insulin-producing cells, which may provide a regenerative strategy of β cells.
2022-01-29 | GSE178726 | GEO
Project description:Natural and stable cell identity switches, where terminally-differentiated cells convert into different cell-types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells become insulin expressers upon ablation of insulin-secreting β-cells, promoting diabetes recovery. Whether human islets also display this plasticity for reconstituting β-like cells, especially in diabetic conditions, remains unknown. Here we show that two different islet non-β-cell types, α- and γ–cells, obtained from deceased non-diabetic or diabetic human donors can be lineage-traced and induced to produce insulin and secrete it in response to glucose. When transplanted into diabetic mice, converted human α-cells reverse diabetes and remain producing insulin even after 6 months. Insulin-producing α-cells maintain α-cell markers, as seen by deep transcriptomic and proteomic characterization, and display hypo-immunogenic features when exposed to T-cells derived from diabetic patients. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity in islet cells, as well as in other organs, as a therapy for degenerative diseases by fostering the highly-regulated intrinsic cell regeneration.
2018-12-13 | GSE117454 | GEO
Project description:Natural and stable cell identity switches, where terminally-differentiated cells convert into different cell-types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells become insulin expressers upon ablation of insulin-secreting β-cells, promoting diabetes recovery. Whether human islets also display this plasticity for reconstituting β-like cells, especially in diabetic conditions, remains unknown. Here we show that two different islet non-β-cell types, α- and γ–cells, obtained from deceased non-diabetic or diabetic human donors can be lineage-traced and induced to produce insulin and secrete it in response to glucose. When transplanted into diabetic mice, converted human α-cells reverse diabetes and remain producing insulin even after 6 months. Insulin-producing α-cells maintain α-cell markers, as seen by deep transcriptomic and proteomic characterization, and display hypo-immunogenic features when exposed to T-cells derived from diabetic patients. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity in islet cells, as well as in other organs, as a therapy for degenerative diseases by fostering the highly-regulated intrinsic cell regeneration.
2018-12-15 | GSE123844 | GEO
Project description:The expression profile of miRNAs in MSCs and differentiated Insulin-producing cells was examined using RNA-seq technology. The expression of 411 miRNAs was observed, which we classified into three groups according to expression levels in differentiated Insulin-producing cells relative to that in MSCs: group I contained 107 miRNAs with an increased level of expression, group II contained 250 miRNAs that showed no change in expression and group III contained 54 miRNAs with decreased levels of expression.
2015-08-20 | GSE72222 | GEO