Investigating Ngn3-expressing cells in the adult mouse pancreas
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE138038 | GEO | 2021/09/02
REPOSITORIES: GEO
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Project description:Investigating Ngn3-expressing cells in the adult mouse pancreas
| PRJNA574278 | ENA
Project description:Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells. We used microarray analysis to detail the global changes in gene expression as Sox9 positive embryonic pancreatic progenitors differentiatiate into adult ductal cells or the endocrine lineage. GFP positive cells from Sox9-EGFP mouse pancreas were isolated by FACS at different stages of development (e10.5, e15.5, and p23) for RNA extraction and hybridization to Affymetrix microarrays. To obtain populations highly enriched in Sox9 expression, we collected only GFP Hi populations for analysis. To identify gene expression changes specific to the differentiation of progenitors to ductal cells or endocrine cells, we also isolated and analyzed the gene expression profile of GFP negative cells isolated at p23, as well as GFP positive cells isolated from Ngn3-EGFP mouse pancreas at e15.5. These two populations allow the identification of genes whose expression is associated with the newly differentiated endocrine progeny in the embryo (Ngn3-GFP positive) and adult acinar and endocrine cells at p23.
2012-08-01 | E-GEOD-34060 | biostudies-arrayexpress
Project description:The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into β-cells. The induced β-cells resemble islet β-cells in morphology and histology, express genes essential for β-cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type. We used microarray to compare adult mouse fbw7 knock out ductal cells with bonafide beta cells In order to isolate fbw7 ko, fbw7 wt ductal cells and beta cells we used adult mice with the following genotypes: MIP-GFP (beta cells are constitutively labelled with GFP), Ck19-CreERT; R26-LSL-YFP; Fbw7 +/+ (ductal cells are labelled with YFP upon tamoxifen injection) and Ck19-CreERT; R26-LSL-YFP; Fbw7 F/F mice (ductal cells are labelled with YFP upon tamoxifen injection). 30000 GFP+ cells were isolated by FACS-sorting. RNA was extracted and amplified using NuGEN kit.
2014-08-07 | E-GEOD-58969 | biostudies-arrayexpress
Project description:Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells. We used microarray analysis to detail the global changes in gene expression as Sox9 positive embryonic pancreatic progenitors differentiatiate into adult ductal cells or the endocrine lineage.
2012-08-02 | GSE34060 | GEO
Project description:Pancreas development involves a coordinated process in which an early phase of cell segregation and patterning is proceeded by a longer phase of lineage restriction, expansion and extensive tissue remodeling. By combining quantitative clonal lineage tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. Our results show that the large-scale organization of tissue can be traced to the activity of self-renewing precursors that localize at the termini of growing ductal branches and act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this process, multipotent precursors give rise to self-renewing acinar-committed precursors, which are conveyed with growing ducts, as well as fate-restricted ductal progenitors that expand the trailing ducts and give rise to delaminating islet precursors. Together, these findings define quantitatively how the functional behavior and lineage progression of heterogeneous pools of the pancreatic precursors that define the organization of the organ.
2017-11-11 | GSE89798 | GEO
Project description:The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into β-cells. The induced β-cells resemble islet β-cells in morphology and histology, express genes essential for β-cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type. We used microarray to compare adult mouse fbw7 knock out ductal cells with bonafide beta cells
2014-08-07 | GSE58969 | GEO
Project description:Previously, we identified tripotent colony-forming progenitor cells in the adult murine pancreas that were capable of self-renewal and differentiation into duct, acinar and endocrine cells in vitro. However, the incidence of these progenitor cells was low (~1% among pancreatic cells in adult 2-4 month-old mice). The goal of the current study was to find cell-surface markers that can distinguish and enrich pancreatic colony-forming progenitor cells. It was found that pancreatic cells could be divided into CD133+CD71- , CD133highCD71low and CD133lowCD71low and CD133-CD71- cells. CD133highCD71low cells, but not other cell populations, were the most enriched for colony-forming progenitors. Interestingly, both CD133+CD71- and CD133highCD71low cells expressed ductal markers as shown by gene expression RT-PCR analysis. To further characterize CD133+CD71- (designated as R1 cells) and CD133highCD71low (designated as R2 cells) ductal cell populations, genome-wide gene expression analysis using RNA-seq was performed. The genes that were differentially expressed by R1 and R2 cells are deposited here. Subsequent pathway analysis of the RNA-seq data revealed that R2 and R1 cells have propensity for cell migration and immune response, respectively. These gene expression analyses suggested ductal cells of the adult pancreas are heterogeneous in nature. Two populations of cells are sorted from the pancreas of adult 2-4 month old C57Bl/6 mice and their RNA profiles are determined. These cell populations are CD133(high)CD71(low) cells (3 samples) and CD133(positive)CD71(negative) (2 samples).
2016-07-03 | E-GEOD-72990 | biostudies-arrayexpress
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 We generated arrays from whole pancreas, islet, acinar and duct (Sox9+ sorted) cells and pancreas derived cultures maintained in our defined medium. For the clustering analysis we substracted the pancreas array to all arrays. Genes 2 fold differentially expressed in the ductal array were used for the analsyis. For the genes enriched in organoid cultures compared to pancreas we substracted the organoid culture arrays to the pancreas array. Genes >2-fold differentially expressed were used for the analysis.
2013-09-17 | E-GEOD-50103 | biostudies-arrayexpress
Project description:Ngn3 is a bHLH transcription factor critical for the specification of endocrine cells in the pancreatic Islets of Langerhans. Previous studies in mouse embryos have reported transient expression of Ngn3 in scattered cells within the developing pancreatic epithelium during midgestation (Schwitzgebel et al. [2000] Development 127:3533-3542). Specifically, these Ngn3-expressing cells have been shown to be progenitor cells fated to give rise to islet endocrine cells (Gradwohl et al. [2000] Proc Natl Acad Sci USA 97:1607-1611). Here, we characterize the expression of Ngn3 transcripts and protein throughout pancreatic development. Interestingly, we identify and define a dramatic and previously unnoticed gap in developmental Ngn3 expression. We show that both Ngn3 transcript and protein expression occur in two distinct temporal waves, the first occurring early from approximately E8.5 to E11.0, and the second initiating at approximately E12.0. Strikingly, this observed biphasic expression correlates with the "first" and "second" transitions, which encompass two distinct waves of embryonic endocrine differentiation. In addition, our studies demonstrate that Ngn3 transcripts are markedly more widespread in the pancreatic epithelium than NGN3 protein, indicating that post-transcriptional regulation is likely to play a critical role during endocrine differentiation.
| S-EPMC2597057 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDA) is the devastating disease in urgent need to identify new strategies for diagnosing and treating. Chronic pancreatitis is a risk factor for PDA in humans. Nardilysin (Nrdc, NRDC), a zinc peptidase of the M16 family has been shown to promote cancer cell growth in vitro. Here, we report that pancreatic deletion of Nrdc dramatically accelerates formation of pancreatic intraepithelial neoplasia (PanIN) and invasive PDA in the presence of oncogenic Kras. Nrdc was expressed in the nucleus of pancreatic acinar cells and pancreatic deletion of Nrdc was dispensable for pancreatic development in mice, but led to spontaneous chronic pancreatitis concomitant with acinar-to-ductal conversion, fibrotic change, infiltrated inflammatory cells, increased apoptosis, and atrophic pancreas in adult mice. Ex vivo acinar cell explants culture experiments showed that acinar-to-ductal conversion was not induced through a cell autonomous mechanism and that expression of several chemokines, including Cxcl10, was markedly up-regulated in Nrdc-null pancreatic acinar cells. Microarray analysis revealed that pathways implicated in pancreatitis and tumorigenesis, including chemotaxis, NF-κB and Erk1/2 signaling, were up-regulated in Nrdc-cKO pancreata compared with WT controls. Finally, immunostaining for NRDC revealed absence of NRDC expression in a subset of human PanINs and PDAs. These data demonstrate a previously unappreciated tumor suppressive function of Nrdc in the pancreas through suppressing chronic pancreatitis with acinar-to-ductal conversion in mice.
2017-05-31 | GSE99438 | GEO