Transcriptional profiling of pancreatic somatostatin and beta-cells from zebrafish [scRNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE152695 | GEO | 2021/12/31
REPOSITORIES: GEO
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Project description:Pancreas contains a collection of different types of endocrine cells. Each endocrine cell secretes a specific hormone. Using reporter lines for two hormones, insulin and somatostatin1.1, we observe the presence of bi-hormonal cells in zebrafish pancreas. To characterize the cells at transcriptional level, we performed next-generation RNA-Sequencing on FACS sorted cells expressing sst1.1, ins, or both sst1.1 and ins.
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Project description:Pancreatic beta cell generation from induced pluripotent stem cells (iPSCs) offers an alternative donor tissue source; however, the efficiency of induction of INSULIN (INS)+ cells from human iPSCs (hiPSCs) is low. We aimed to establish an efficient differentiation protocol for generating INS+ cells from hiPSCs by identifying novel inducers. We screened small molecules that increased the induction rate of INS+ cells from hiPSC-derived PDX1+ pancreatic progenitor cells by using high-throughput screening (HTS) system. We identified one compound, sodium cromoglicate (SCG) out of about 1,250 small molecules that we screened. When SCG was combined with the previously described protocol, the induction rate of INS+ cells increased up to 15–20%, and the cells developed the ability to secrete C-peptide in vitro. We found that SCG facilitates the differentiation of multiple endocrine cell types, including INS+ cells, in both hiPSC differentiation cultures and mouse embryonic pancreas explants by inducing NEUROG3+ endocrine precursor cells. We also confirmed that the mechanisms of action by which SCG induces the pancreatic endocrine differentiation include the inhibition of BMP4 signaling.
2018-05-10 | GSE89973 | GEO
Project description:The enteroendocrine lineage secretes hormones which direct the digestion, absorption, and motility of the intestine. Arx is a transcription factor expressed specifically in the enteroendocrine cells. With intestinal-specific loss of Arx, hormonal expression is disrupted. We used microarrays to determine the differential expression of genes from the whole duodenum after removal of Arx, a gene specifically expressed in the enteroendocrine lineage, in the intestinal epithelium compared to littermate controls at postnatal day 5.
2017-12-08 | GSE107828 | GEO
Project description:deBack2012 - Lineage Specification in Pancreas Development
This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells.
This model is described in the article:
On the role of lateral stabilization during early patterning in the pancreas
de Back W., Zhou JX, Brusch L
J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766
Abstract:
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
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2024-09-02 | BIOMD0000000435 | BioModels
Project description:Endocrine cells employ regulated exocytosis of secretory granules to secrete hormones and neurotransmitters. Secretory granule exocytosis depends on spatio-temporal variables such as proximity to the plasma membrane and age, with newly-generated granules being preferentially released. Despite recent advances, we lack a comprehensive view about the molecular composition of insulin granules and associated changes over their lifetime. Here we report a strategy for the purification of insulin secretory granules of distinct age from insulinoma INS-1 cells. Tagging the granule-resident protein phogrin with a cleavable CLIP tag, we obtain intact fractions of age-distinct granules for proteomic and lipidomic analyses. We find that the lipid composition changes
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Project description:Insulinomas (INS) are rare pancreatic endocrine tumours (PETs), arising from tumoral beta-cells from the pancreatic islets of Langerhans. Canine INS are malignant in >95% of cases. This study aims to provide further insights on molecular pathways involved in INS pathogenesis and to identify prognostic genes. Canine specific cDNA microarray representing 20,313 genes was used to analyze expression profiles in a panel of ten primary INS and ten INS metastases. Eighty-four genes were found to be significantly down-regulated in the group of metastases in comparison to the group of primary INS. From the microarray analysis it also followed that primary INS, based on their gene expression profiles, can be divided into two groups, which differ in their malignancy potential. It was also demonstrated that canine INS have both endocrine and exocrine cell features. Furthermore, the present study has revealed pancreatic lipase and chymotrypsinogen B1 as candidate genes that can be followed up in prospective studies as prognostic markers for INS. Our findings add to the current knowledge of INS pathogenesis and tumor progression, which can be used for future therapeutic and prognostic strategies, for both dogs and humans.
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Project description:Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5+ stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signaling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by Partial Duct Ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) which expand 5-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality
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