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https://www.readbyqxmd.com/read/29157981/foxo1-inhibition-promotes-differentiation-of-human-embryonic-stem-cells-into-insulin-producing-cells
#1
Fei Yu, Rui Wei, Jin Yang, Junling Liu, Kun Yang, Haining Wang, Yiming Mu, Tianpei Hong
Insulin-producing cells (IPCs) derived from human embryonic stem cells (hESCs) hold great potential for cell transplantation therapy in diabetes. Tremendous progress has been made in inducing differentiation of hESCs into IPCs in vitro, of which definitive endoderm (DE) protocol mimicking foetal pancreatic development has been widely used. However, immaturity of the obtained IPCs limits their further applications in treating diabetes. Forkhead box O1 (FoxO1) is involved in the differentiation and functional maintenance of murine pancreatic β cells, but its role in human β cell differentiation is under elucidation...
November 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29142904/kras-g12d-upregulates-notch-signaling-to-induce-gallbladder-tumorigenesis-in-mice
#2
Wen-Cheng Chung, Junqing Wang, Yunyun Zhou, Keli Xu
Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context. Methods: We determined Cre recombination activity of Pdx1-Cre in the gallbladder using a reporter strain and examined gallbladder tumor development in the Kras(LSL- G12D/+);Pdx1-Cre mice...
September 2017: Oncoscience
https://www.readbyqxmd.com/read/29118967/cold-perfusion-decellularization-of-whole-organ-porcine-pancreas-supports-human-fetal-pancreatic-cell-attachment-and-expression-of-endocrine-and-exocrine-markers
#3
Erik Elebring, Vijay K Kuna, Niclas Kvarnström, Suchitra Sumitran-Holgersson
Despite progress in the field of decellularization and recellularization, the outcome for pancreas has not been adequate. This might be due to the challenging dual nature of pancreas with both endocrine and exocrine tissues. We aimed to develop a novel and efficient cold-perfusion method for decellularization of porcine pancreas and recellularize acellular scaffolds with human fetal pancreatic stem cells. Decellularization of whole porcine pancreas at 4°C with sodium deoxycholate, Triton X-100 and DNase efficiently removed cellular material, while preserving the extracellular matrix structure...
January 2017: Journal of Tissue Engineering
https://www.readbyqxmd.com/read/29118817/maternal-high-fat-diet-impairs-glucose-metabolism-%C3%AE-cell-function-and-proliferation-in-the-second-generation-of-offspring-rats
#4
Yan-Hong Huang, Ting-Ting Ye, Chong-Xiao Liu, Lei Wang, Yuan-Wen Chen, Yan Dong
Background: This study aimed to assess the impact of perinatal high-fat (HF) diet in female Sprague-Dawley rats (F0) on glucose metabolism and islet function in their early life of second-generation of offspring (F2). Methods: F0 rats were fed with a standard chow (SC) or HF diet for 8 weeks before mating, up to termination of lactation for their first-generation of offspring (F1-SC and F1-HF). F1 females were mated with normal males at the age of week 11, and producing F2 offspring (F2-SC, F2-HF)...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29117231/human-pancreatic-islet-derived-extracellular-vesicles-modulate-insulin-expression-in-3d-differentiating-ipsc-clusters
#5
Diana Ribeiro, Eva-Marie Andersson, Nikki Heath, Anette Persson-Kry, Richard Collins, Ryan Hicks, Niek Dekker, Anna Forslöw
It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs) were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC) clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/29107594/genes-associated-with-pancreas-development-and-function-maintain-open-chromatin-in-ipscs-generated-from-human-pancreatic-beta-cells
#6
Matthias Thurner, Liraz Shenhav, Agata Wesolowska-Andersen, Amanda J Bennett, Amy Barrett, Anna L Gloyn, Mark I McCarthy, Nicola L Beer, Shimon Efrat
Current in vitro islet differentiation protocols suffer from heterogeneity and low efficiency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from fibroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identified ∼8.3k significant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were significantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29107069/the-species-origin-of-the-cellular-microenvironment-influences-markers-of-beta-cell-fate-and-function-in-endoc-%C3%AE-h1-cells
#7
N Jeffery, S Richardson, C Beall, L W Harries
Interaction between islet cell subtypes and the extracellular matrix influences beta-cell function in mammals. The tissue architecture of rodent islets is very different to that of human islets; cell-to-cell communication and interaction with the extracellular matrix may vary between species. In this work, we have compared the responses of the human EndoC-βH1 cell line to non-human and human-derived growth matrices in terms of growth morphology, gene expression and glucose-stimulated insulin secretion (GSIS)...
October 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29096722/pdx1-neurogenin-3-and-mafa-critical-transcription-regulators-for-beta-cell-development-and-regeneration
#8
REVIEW
Yaxi Zhu, Qian Liu, Zhiguang Zhou, Yasuhiro Ikeda
Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells...
November 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29093682/salidroside-a-natural-antioxidant-improves-%C3%AE-cell-survival-and-function-via-activating-ampk-pathway
#9
Linjie Ju, Xiaohua Wen, Chunjun Wang, Yingjie Wei, Yunru Peng, Yongfang Ding, Liang Feng, Luan Shu
Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29079704/mitochondrial-protein-ucp2-controls-pancreas-development
#10
Benjamin Broche, Selma Ben Fradj, Esther Aguilar, Tiphaine Sancerni, Matthieu Bénard, Fatna Makaci, Claire Berthault, Raphaël Scharfmann, Marie-Clotilde Alves-Guerra, Bertrand Duvillié
The mitochondrial carrier UCP2 belongs to the family of the uncoupling proteins. Despite its name, it is now accepted that UCP2 is rather a metabolite transporter than an uncoupling protein. UCP2 can regulate oxidative stress and/or energetic metabolism. In rodents, UCP2 is involved in the control of alpha- and beta-cell mass as well as insulin- and glucagon-secretion. Our aim was to determine whether the effects of UCP2 observed on beta-cell mass have an embryonic origin. Thus, we used Ucp2 knock-out mice...
October 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29061659/area-iv-knockout-reveals-how-pdx1-is-regulated-in-postnatal-%C3%AE-cell-development
#11
Aaron R Cox, Jake A Kushner
No abstract text is available yet for this article.
November 2017: Diabetes
https://www.readbyqxmd.com/read/29051265/regulation-of-notch-signaling-by-rab7-and-rab8-requires-carboxyl-methylation-by-icmt
#12
Helen Court, Ian M Ahearn, Marc Amoyel, Erika A Bach, Mark R Philips
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-Kras(G12D) mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency...
October 19, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29050937/integrated-expression-profiling-of-potassium-channels-identifys-kcnn4-as-a-prognostic-biomarker-of-pancreatic-cancer
#13
Shuheng Jiang, Lili Zhu, Jianyu Yang, Lipeng Hu, Jianren Gu, Xin Xing, Yongwei Sun, Zhigang Zhang
Dysregulated potassium (K(+)) channels have previously been shown to promote the development and progression of many types of cancers. Meanwhile, K(+) channels are particularly important in regulating the endocrine and exocrine functions of pancreas. However, the expression pattern and prognostic significance of K(+) channels in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, by screening a GEO dataset containing 36 microdissected PDAC and matching normal pancreatic tissue samples, four differentially expressed K(+) channels (KCNJ5, KCNJ16, KCNN4 and KCNK1) were identified in PDAC...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28988715/self-transducible-bimodal-pdx1-foxp3-protein-lifts-insulin-secretion-and-curbs-autoimmunity-boosting-tregs-in-type-1-diabetic-mice
#14
Christina Amatya, Ilian A Radichev, Jacob Ellefson, Mark Williams, Alexei Y Savinov
Type 1 diabetes (T1D) is characterized by massive destruction of insulin-producing β cells by autoreactive T lymphocytes, arising via defective immune tolerance. Therefore, effective anti-T1D therapeutics should combine autoimmunity-preventing and insulin production-restoring properties. We constructed a cell-permeable PDX1-FOXP3-TAT fusion protein (FP) composed of two transcription factors: forkhead box P3 (FOXP3), the master regulator of differentiation and functioning of self-tolerance-promoting Tregs, and pancreatic duodenal homeobox-1 (PDX1), the crucial factor supporting β cell development and maintenance...
September 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28973544/loss-of-the-imprinted-non-coding-snord116-gene-cluster-in-the-interval-deleted-in-the-prader-willi-syndrome-results-in-murine-neuronal-and-endocrine-pancreatic-developmental-phenotypes
#15
Lisa Cole Burnett, Gabriela Hubner, Charles LeDuc, Michael V Morabito, Jayne F Martin Carli, Rudolph L Leibel
Global neurodevelopmental delay is a prominent characteristic of individuals with Prader-Willi syndrome (PWS). The neuromolecular bases for these delays are unknown. We identified neuroanatomical changes in the brains of mice deficient for a gene in the minimal critical deletion region for PWS (Snord116p-/m+). In Snord116p-/m+ mice, reduced primary forebrain neuron cell body size is apparent in embryonic day 15.5 fetuses, and persists until postnatal day 30 in cerebellar purkinje neurons. Snord116 is a snoRNA gene cluster of unknown function that can localize to the nucleolus...
September 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28951630/identification-of-biomarkers-for-predicting-lymph-node-metastasis-of-stomach-cancer-using-clinical-dna-methylation-data
#16
Jun Wu, Yawen Xiao, Chao Xia, Fan Yang, Hua Li, Zhifeng Shao, Zongli Lin, Xiaodong Zhao
BACKGROUND: Lymph node (LN) metastasis was an independent risk factor for stomach cancer recurrence, and the presence of LN metastasis has great influence on the overall survival of stomach cancer patients. Thus, accurate prediction of the presence of lymph node metastasis can provide guarantee of credible prognosis evaluation of stomach cancer patients. Recently, increasing evidence demonstrated that the aberrant DNA methylation first appears before symptoms of the disease become clinically apparent...
2017: Disease Markers
https://www.readbyqxmd.com/read/28941456/pdx1-a-unique-pancreatic-master-regulator-constantly-changes-its-functions-during-embryonic-development-and-progression-of-pancreatic-cancer
#17
REVIEW
T V Vinogradova, E D Sverdlov
Multifunctional activity of the PDX1 gene product is reviewed. The PDX1 protein is unique in that being expressed exclusively in the pancreas it exhibits various functional activities in this organ both during embryonic development and during induction and progression of pancreatic cancer. Hence, PDX1 belongs to the family of master regulators with multiple and often antagonistic functions.
August 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#18
Jinghai Wu, Xin Liu, Sunayana G Nayak, Jason R Pitarresi, Maria C Cuitiño, Lianbo Yu, Blake E Hildreth, Katie A Thies, Daniel J Schilling, Soledad A Fernandez, Gustavo Leone, Michael C Ostrowski
The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression...
2017: PloS One
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#19
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28931935/alpha-tc1-and-beta-tc-6-genomic-profiling-uncovers-both-shared-and-distinct-transcriptional-regulatory-features-with-their-primary-islet-counterparts
#20
Nathan Lawlor, Ahrim Youn, Romy Kursawe, Duygu Ucar, Michael L Stitzel
Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements...
September 20, 2017: Scientific Reports
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