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Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More Beta-Cell Production

ABSTRACT: Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for b-cell loss since their b-cell–producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that b-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward b-cells in mouse and human. These effects are dynamic and correlate with functional b-cell regeneration when conditions allow.

ORGANISM(S): Mus musculus

PROVIDER: GSE66817 | GEO | 2015/03/13

SECONDARY ACCESSION(S): PRJNA278022

REPOSITORIES: GEO

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Gene expression signatures for PMP treatment

Project description:To identify the genes inversely regulated by PMPs, we performed a microarray for global gene expression profiling in CB-MNCs with/without PMP treatment. In MNCs treated with PMPs, 129 genes were downregulated.

2020-09-07 | GSE152079 | GEO

Expression data from RA-FLSs with PMPs

Project description:Platelet microparticles (PMPs) are closely related to the activity of rheumatoid arthritis, and promote the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). In order to identify the possible mechanisms of the promotion effect on migration and invasion of RA-FLS by PMP, we used microarray analysis to detect the gene expressions of RA-FLSs after treatment with PMPs.

2017-06-06 | GSE99681 | GEO

Plasma membrane proteome of adhesion-competent endometrial epithelial cells and its modulation by Rab11a

Project description:Human endometrial epithelium (EE) is composed of a multitude of proteins, amongst which those localized on the plasma membrane (plasma membrane proteins-PMPs) are of critical relevance in early stages of implantation. Evidences support the key role of few PMPs in implantation. However, many remain unidentified, as efforts have not been made till date to generate the plasma membrane proteome of human EE cells, using a gel-free approach. This study presents a protein catalogue of the PMP enriched fraction of Ishikawa cell line; often used as an in vitro model for embryo-adhesive EE. Liquid Chromatography with tandem mass spectrometry identified 3598 proteins. Of these, 1963 proteins were annotated for their membrane localization. Of 1963 proteins, 1321 were found to have transmembrane domain and 43 proteins had GPI anchor. Extensive data mining revealed endometrial expression of 943 proteins reported in human and/or rodents. Further, quantitative alterations were observed in the plasma membrane proteome on perturbation of intracellular trafficking. Silencing of Rab11a (known for its role in plasma membrane organization) expression caused alteration in the abundance of 74 proteins. Caveolin-1 and EpCAM levels were reduced whereas Rab4a abundance increased in the PMP extracts of Rab11a-deficient cells, compared to control cells. Briefly, the study reports the identity of several novel plasma membrane-localized proteins. A major spin-off of the study is the identification of novel proteins trafficked by Rab11a to the plasma membrane. Targeted analysis of novel PMPs may reveal their specific roles in endometrial receptivity and implantation.

2019-11-08 | PXD015010 | Pride

miRNA expression of the isolated human platelet-derived microparticle

Project description:To analysis of potential functional components in PMPs to miRNAs, we have employed miRNA microarray expression profiling as a discovery platform to identified the miRNA content of PMPs.Human cord blood from healthy donors was used to isolated platelets and platelet-derived microparticles (PMPs) were isolated from activated platelets. First, for platelet isolation and purification, human platelets were isolated from the supernatant of umbilical cord blood after Ficoll-Hypaque density gradient centrifugation and pelleted by centrifugation at 2,000 × g for 20 min at RT. Second, the platelets were resuspended in saline (pH=7.4) containing 1 mM calcium and 1 U per mL thrombin for 15 min at 37°C. The PMPs were released into the supernatant. Contaminating remnant platelets were removed by centrifugation at 2,000 × g for 20 min at 4°C and filtered through a 0.8 μm filter unit (Millipore, America). Then, the supernatants containing PMPs were centrifuged at 20,000 × g for 120 min at 4°C.182 miRNAs were detected in the isolated human PMPs from five independent donors, although individual differences in miRNA expression were also observed. Thereafter, these miRNAs were ranked by expression level, and those expressed above the median level from each unique subject were considered to be abundantly expressed miRNAs. The intersection of abundantly expressed miRNAs in PMPs from each donor yielded 48 commonly expressed miRNAs in PMPs. Among these 48 miRNAs, miR-4454 ranked number 1, and its level was consistent in all samples examined.

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Project description: Not available

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Peroxisome function relies on organelle-associated mRNA translation

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Global gene expression and Stromal contents improve prognostic power in PMP patients treated by CRS+HIPEC

Project description:In recent years, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have substantially improved the clinical outcome of pseudomyxoma peritonei (PMP) originating from mucinous appendiceal cancer. However, current histopathological grading of appendiceal PMP frequently fails in predicting disease outcome. We recently observed that the integration of cancer cell transcriptional traits with those of cancer-associated fibroblasts (CAFs) improves prognostic prediction for tumors of the large intestine. We therefore generated global expression profiles on a consecutive series of 24 PMP patients treated with CRS plus HIPEC. Multiple lesions were profiled for nine patients. We then used expression data to stratify the samples by a previously published "high-risk appendiceal cancer" (HRAC) signature and by a CAF signature that we previously developed for colorectal cancer, or by a combination of both. The prognostic value of the HRAC signature was confirmed in our cohort and further improved by integration of the CAF signature. Classification of cases profiled for multiple lesions revealed the existence of outlier samples and highlighted the need of profiling multiple PMP lesions to select representative samples for optimal performances. The integrated predictor was subsequently validated in an independent PMP cohort. These results provide new insights into PMP biology, revealing a previously unrecognized prognostic role of the stromal component and supporting integration of standard pathological grade with the HRAC and CAF transcriptional signatures to better predict disease outcome.

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?-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates.

Project description: Not available

| S-EPMC4447363 | biostudies-literature

Profiling of gene expression in TLR2 and TLR3 activated macrophages

Project description:We have identified more than 50 genes that have upregulated expression in TLR3 activated (PMI-1,2), but have downregulated expression in TLR2 activated (PMP-1,2) macrophages, as compared to control cells (PMC-1,2) identify genes that have upregulated expression in TLR3 activated (PMI-1,2), but have downregulated expression in TLR2 activated (PMP-1,2) macrophages, as compared to control cells (PMC-1,2)

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miRNA expression profiles of Platelet microparticles (PMPs)

Project description:To identify the miRNA expressing profiles of Platelet microparticlesï¼PMPs, we have employed the Agilent Human miRNA 8Ã60K (Design ID:046064) microarray. Platelet microparticles. The platelets were derived from citrated blood of healthy human donors under an Institutional Review Board-approved protocol. Platelets were isolated after centrifugation of blood (1200r for 30 min at 21â), then the supernatant (platelet-rich plasma) was centrifuged at 2000r for 30 min at 21â, and the pellet containing platelets was resuspended in RPMI-1640 medium (HyClone, Logan, UT). Platelets were counted (Clinical Laboratory, Shanghai First Maternity and Infant Hospital, Shanghai) and adjusted to a density of 150 Ã 106 cells/mL before supplement with 1.5% ACD(sigma ) and stimulated with thrombin (1.0 u/mL; Takeda Austria) for 1 h. PMPs were in the supernatant after centrifugation at 4000r for 10 min at 4â,then the supernatants were centrifuged at 50,000 Ã g for 60 min at 4 Â°C. The pellets containing MPs were resuspended in RPMI-1640 medium and quantified by BCA method. The gene expressions of three independent paired PMPs from platelets stimulated by thrombin or apoptosis.

2016-01-14 | E-GEOD-76789 | biostudies-arrayexpress

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