Expression analysis of BMP7 responsive P2RY1/ALK3 expressing progenitor like cells within the human exocrine pancreas
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PROVIDER: PRJNA408303 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Here we demonstrate ALK3Bright/PDX1+ cells residing within the human pancreatic ducts have progenitor like characteristics. Using flow cytometery, live-cell sorting of ALK3bright/PDX1+ cells is possible using a surrogate surface marker for PDX1 (P2RY1). Treating ALK3bright/P2RY1+ cells with BMP7 results in their expansion. Later removal of BMP7 results in the differentiation of these cells to β-like cells. Here we compare the mRNA expression profiles of these three different cell types (in triplicate). Methods: mRNA profiles of ALK3Bright/P2RY1+ cells isolated from human non-endocrine pancreatic tissue, ALK3Bright/P2RY1+ cells treated with BMP7 and ALK3Bright/P2RY1+ cells differentiated to β-like cells after BMP7 removal were generated by deep sequencing, in triplicate, using Illumina HiSeq PE Cluster Kit v4 and Illumina HiSeq Flow Cell v4 with 50 nt paired end reads plus dual index reads using the Illumina HiSeq SBS kit v4. Sequence reads that passed quality filters were analyzed at the transcript isoform level following alignment using TopHat v2.1.0 followed by exon and gene level counting using Bioconductor easyRNASeq v 2.4.7. Conclusions: Our study represents the first detailed analysis of ALK3Bright/P2RY1+ sorted cells with biological replicates. We demonstrate ALK3Bright/P2RY1+ cells were shown to form progenitor-like epithelial colonies characterized by NKX6.1 and PDX1 expression. Unlike the negative fraction controls, these colonies responded to BMP-7 by generating new β-like cells as well as cells from other pancreatic lineages. The transcriptional profile of these cells and their BMP7 treated counterparts suggest a mitotic and progenitor like state. Our studies confirm the progenitor-like nature of ALK3Bright/PDX1+ cells within the human pancreas and suggest a specific anatomical location within the ductal network.
2018-02-08 | GSE104120 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE34030: LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function [RNA-Seq] GSE34295: LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function [ChIP-Seq] Refer to individual Series
2011-12-09 | E-GEOD-34296 | biostudies-arrayexpress
Project description:We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in the exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochrondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulationg exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid. input and Lrh1 ChIP
2011-12-09 | E-GEOD-34295 | biostudies-arrayexpress
Project description:Early postnatal overnutrition causes persistent dysregulation of endocrine pancreas function. We used genome-scale DNA methylation profiling in the suckling-period small litter (SL) mouse model to test whether this occurs via persistent epigenetic changes in pancreatic islets. Although SL islets showed DNA methylation changes directly after weaning and in adulthood, few of these were present at both ages, contrary to our hypothesis. Most interestingly, we discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging. Focusing on a subset of genes relevant to β cell function, we showed that these methylation differences are strongly correlated with expression. Together, our results provide the novel insight that DNA methylation changes that occur as islets age indicate an overall epigenetic drift toward the exocrine pancreas epigenome. These concerted shifts in the islet methylome could contribute to the age-associated decline in endocrine pancreas function. Pancreatic islets were isolated from P21/P180 SL or C mice. To ensure purity of islets, 3 rounds of manual picking were performed in each samples. Whole pancreas samples, ~98% of which is exocrine pancreas, were used as exocrine pancreas. There are 5 mice per group.
2014-12-03 | E-GEOD-63811 | biostudies-arrayexpress
Project description:Molecular characterization of PERK's role in the mouse exocrine pancreas. Postnatal days 16, 19 and 32 were examined. Postnatal day 16 represents a stage immediately prior to severe cytological changes in the exPKO mice. Postnatal day 19 represents the initial stage of severe phenotypes in the exPKO mice. Postnatal day 32 represents the middle stage of severe phenotypes (about 2 wks from the initiation) in the exPKO mice. Keywords: transgenic mouse
2007-08-01 | GSE4422 | GEO
Project description:We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in the exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochrondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulationg exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid.
2011-12-09 | GSE34295 | GEO
Project description:Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized. Here, we used scRNA-seq to comprehensively characterize mouse ductal heterogeneity at single-cell resolution of the entire ductal epithelium from centroacinar cells to the main duct. Moreover, we used organoid cultures, injury models and pancreatic tumor samples to interrogate the role of novel ductal populations in pancreas regeneration and exocrine pathogenesis. In our study, we have identified the coexistence of 15 ductal populations within the healthy pancreas and characterized their organoid formation capacity and endocrine differentiation potential. Cluster isolation and subsequent culturing let us identify ductal cell populations with high organoid formation capacity and endocrine and exocrine differentiation potential in vitro, including Wnt-responsive-population, ciliated-population and FLRT3+ cells. Moreover, we have characterized the location of these novel ductal populations in healthy pancreas, chronic pancreatitis and tumor samples, hightlihgting a putative role of WNT-responsive, IFN-responsive and EMT-populations in pancreatic exocrine pathogenesis as their expression inceases in chronic pancreatitis and PanIN lesions. In light of our discovery of previously unidentified ductal populations, we unmask the potential roles of specific ductal populations in pancreas regeneration and exocrine pathogenesis.
2024-03-24 | GSE262292 | GEO
Project description:Several miRNAs have tissue-specific patterns consistent with crucial functions in many biological processes and are candidate biomarkers of disease. Yet, there is limited knowledge about the role of pancreas-specific miRNAs in pancreatic pathologies. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. By profiling miRNAs from human islets and subsequent systematic tissue analysis we found that miR-216a is highly enriched in endocrine and exocrine pancreas. Deletion of miR-216a in mice lead to a reduction in islet size, β-cell mass and insulin levels. RNA-sequencing indicated that cell cycle and proliferation were the most significantly regulated biological processes in miR-216 knockout pancreata. miR-216a was induced by TGF-β signalling and inhibition of miR-216a increased apoptosis and decreased cell proliferation in both β- and exocrine cells. Deletion of miR-216a in the pancreatic cancer prone mouse line Kras G12D ;Ptf1a CreER reduced the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels were elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA but also suggests miR-216a as a promising biomarker for diagnosis of pancreatic diseases.
2021-10-22 | GSE159844 | GEO
Project description:The purpose of this study was to identify mRNA transcripts encoding tissue restricted cell surface proteins on human islet tissue that, in turn, might serve as markers for determination of healthy, transplanted and/or diseased islet cell mass. Using oligonucleotide microarrays and clinical grade human islets, we obtained the gene expression profiles of cultured normal islet tissue and compared them to profiles of islets treated with interferon alpha 2 beta, islet-depleted exocrine pancreas, pooled whole pancreas, pooled liver and pooled kidney tissue. Data set filtering and comparisons of gene expression patterns revealed a small set of genes corresponding to transmembrane or membrane associated proteins with limited tissue distributions (present in Islets of Langerhans and, often, central or peripheral nervous system tissues, but absent from exocrine pancreas, liver, kidney and other tissues) with possible utility as novel islet markers. Under the influence of IFN alpha, some of these transcripts show differential expression as confirmed by real time PCR. In addition, we found significant differential expression of two sets of transcripts expressed in islets but with broad tissue distributions, non classical MHC class I b (HLA-G and F) and MHC Class II locus (e.g. HLA-DR alpha and HLA-DQ alpha and beta).
2007-04-06 | E-CBIL-27 | biostudies-arrayexpress
Project description:Several miRNAs have tissue-specific patterns consistent with crucial functions in many biological processes and are candidate biomarkers of disease. Yet, there is limited knowledge about the role of pancreas-specific miRNAs in pancreatic pathologies. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. By profiling miRNAs from human islets and subsequent systematic tissue analysis we found that miR-216a is highly enriched in endocrine and exocrine pancreas. Deletion of miR-216a in mice lead to a reduction in islet size, β-cell mass and insulin levels. RNA-sequencing indicated that cell cycle and proliferation were the most significantly regulated biological processes in miR-216 knockout pancreata. miR-216a was induced by TGF-β signalling and inhibition of miR-216a increased apoptosis and decreased cell proliferation in both β- and exocrine cells. Deletion of miR-216a in the pancreatic cancer prone mouse line Kras G12D ;Ptf1a CreER reduced the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels were elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA but also suggests miR-216a as a promising biomarker for diagnosis of pancreatic diseases.
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