Similar Datasets
Project description:We employed single-cell RNA sequencing of islets in young mice subjected to partial pancreatectomy (PPTx). Four clusters of pancreatic beta cells including a subpopulation of replicating beta cells. Pseudo-time course analysis clarified the gradual changes in gene expression from non-replicating beta cells to replicating ones. Upstream analysis visualized the transcriptional networks associated with beta cell replication by PPTx.
2020-11-04 | GSE152731 | GEO
Project description:Sequencing discerns sub-populations of pancreatic β-cells and dynamics of gene expression in partial pancreatectomy model
| PRJNA640286 | ENA
Project description:RNA sequencing discerns sub-populations of pancreatic β-cells and dynamics of gene expression in partial pancreatectomy model
| PRJNA640291 | ENA
Project description:Heterogeneity of gene expression and rarity of replication hamper molecular analysis of β-cell mass restoration in adult pancreas. Here, we show transcriptional dynamics in β-cell replication process by single-cell RNA sequencing of murine pancreas with or without partial pancreatectomy. We observed heterogeneity of Ins1-expressing β-cells and identified the one cluster as replicating β-cells with high expression of cell proliferation markers Pcna and Mki67. We also recapitulated cell cycle transition accompanied with switching expression of cyclins and E2F transcription factors. Both transient activation of endoplasmic reticulum stress responders like Atf6 and Hspa5 and elevated expression of tumor suppressors like Trp53, Rb1, and Brca1 and DNA damage responders like Atm, Atr, Rad51, Chek1, and Chek2 during the transition to replication associated fine balance of cell cycle progression and protection from DNA damage. Taken together, these results provide a high-resolution map depicting a sophisticated genetic circuit for replication of the β-cells.
| S-EPMC7689163 | biostudies-literature
Project description:We employed single-cell RNA sequencing of islets in young mice subjected to partial pancreatectomy (PPTx). Four clusters of pancreatic beta cells including a subpopulation of replicating beta cells. Pseudo-time course analysis clarified the gradual changes in gene expression from non-replicating beta cells to replicating ones. Upstream analysis visualized the transcriptional networks associated with beta cell replication by PPTx.
2020-11-04 | GSE152730 | GEO
Project description:Background and objectivesMechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined.MethodsPancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection.ResultsIn remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment.ConclusionaPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.
| S-EPMC5147817 | biostudies-literature
Project description:17?-Estradiol (E2) is a multifunctional steroid hormone in modulating metabolism in vivo. Previous studies have reported that E2 could promote insulin secretion and protect ? cells from apoptosis. In this study, the partial pancreatectomy (PPx) model was used to study the role of E2 in islet cell proliferation. The animals were divided into four groups, including sham control, PPx model, E2, and E2 plus estrogen antagonist (E2 plus ICI) groups. In the E2 group, 5-bromo-2'-deoxyuridine- and Ki67-positive cells significantly increased after PPx, and the protein expression of forkhead transcription factor M1, cyclin A2, cyclin B1, and cyclin E2 also significantly increased in the isolated islets. The messenger RNA expression of cyclin A2 and cyclin B2 increased in E2 treatment group. Additionally, the effects of E2 on the PPx mice were partially blocked by estrogen antagonist ICI182,780. The results indicated that E2 significantly promoted islet cell proliferation in PPx model mice, and it upregulated the expression of cell cycle genes. In conclusion, E2 treatment is beneficial for islet cell proliferation in adult mice after PPx. A partial pancreatectomy in mice may be an attractive model for the study of islet cell proliferation.
| S-EPMC5686603 | biostudies-literature
Project description:Single-cell Transcriptome Analysis Dissects the Replicating Process of Pancreatic Beta Cells in Partial Pancreatectomy Model.
| PRJNA640290 | ENA
Project description:ObjectiveThis study was designed to determine whether the transcription factor FoxM1 was required for regeneration of beta-cell mass via proliferation and/or neogenesis in the adult after 60% partial pancreatectomy (PPx).Research design and methodsAdult mice with a pancreas-wide deletion of Foxm1 (Foxm1(flox/flox);Pdx1-Cre [FoxM1(Deltapanc)]) and their control littermates (Foxm1(flox/flox)) were subjected to PPx or a sham operation, after which islet expression of Foxm1 and several target genes, beta-cell mass, proliferation, beta-cell size, islet size, islet density, and neurogenin-3 expression were analyzed.ResultsIn control mice, PPx stimulated beta-cell proliferation and neogenesis and upregulated Foxm1 and several of its known targets (Plk1, Cenp-a, Birc5/Survivin, and Ccnb1) in islets. Within 1 week post-PPx, control mice underwent significant regeneration of beta-cell mass, and average islet size within the regenerating lobe was similar to that after a sham operation. However, FoxM1(Deltapanc) mice exhibited specific impairments in beta-cell mass regeneration and islet growth after PPx, with reduced proliferation of alpha- and beta-cells but no impairments in acinar or ductal cell proliferation. Interestingly, FoxM1 was not required for proliferation of beta-cells within small endocrine cell clusters located in the regenerating portion of the pancreas but was specifically required for proliferation of beta-cells within larger islets. Additionally, FoxM1 was not required for beta-cell neogenesis following PPx.ConclusionsOur results indicate that FoxM1 is partially required for increased beta-cell proliferation, but not beta-cell neogenesis, stimulated by PPx. Furthermore, FoxM1 seems to be dispensable for proliferation of beta-cells following neogenesis but is required for proliferation of preexisting beta-cells.
| S-EPMC2570403 | biostudies-literature
Project description:BackgroundTotal pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations.MethodsThe study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis.ResultsFor all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05).ConclusionsCompared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.
| S-EPMC9201187 | biostudies-literature