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.
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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.
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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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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:Somatostatin (SST) is a cyclic peptide that is understood to inhibit the release of hormones and neurotransmitters from a variety of cells by binding to one of five canonical G protein-coupled SST receptors (SSTR1 to SSTR5). Recently, SST was observed to also interact with the amyloid beta (Aβ) peptide and affect its aggregation kinetics, raising the question which other brain proteins it can bind to. Here we report on an SST interactome analysis that made use of human brain extracts as biological source material and incorporated advanced mass spectrometry workflows for the relative quantitation of binders.
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