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Blood vessels restrain pancreas branching, differentiation and growth

ABSTRACT: How organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE32098 | GEO | 2011/09/14

SECONDARY ACCESSION(S): PRJNA147551

REPOSITORIES: GEO

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Blood vessels restrain pancreas branching, differentiation and growth

Project description:How organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells. For transcriptome analysis, RNA was isolated using QIAGEN RNeasy micro Kit from pancreatic buds of Pdx1-tTA (n=3) and littermate Pdx1-tTA; TET-VEGF (n=3) e12.5 embryos, or from e12.5 wild type pancreatic buds explanted and treated with VEGFR2i (n=5) or vehicle (n=5) for 2 days. Pooled samples were hybridized to Affymetrix mouse gene 1.0 st arrays. The arrays were RMA normalized using Partek Genomic Suite 6.5. Differentially regulated genes were selected based on p-values and ratios using t-test.

2011-09-13 | E-GEOD-32098 | biostudies-arrayexpress

Mus musculus

Project description:Blood vessels restrain pancreas branching, differentiation and growth

| PRJNA147551 | ENA

Blood vessels restrain pancreas branching, differentiation and growth.

Project description: Not available

| S-EPMC4496872 | biostudies-other

Expression data from collecting lymphatic vessels

Project description:Lymphogenous metastasis is an important event in the progression of many human cancers, and is associated with expression of vascular endothelial growth factor-D (VEGF-D). Changes to the lymphatic vasculature can occur during metastasis, and may aid metastatic spread. We investigated the effect of tumour derived VEGFD on the endothelium of the collecting lymphatic vessels draining primary tumors. We used microarrays to detail the changes in gene expression in the collecting lymphatic endothelium of mice with 293EBNA xenografts compared to 293EBNA xenografts overexpressing VEGFD. Mice were injected with 293EBNA cells (transfected with either empty APEX vector, or vector containing VEGFD) and tumours were allowed to grow to size. Mice were sacrificed and collecting lymphatic vessels were dissected. The endothelial cell population was isolated and RNA was extracted and hybridized on Affymetrix microarrays.

2012-01-15 | E-GEOD-34135 | biostudies-arrayexpress

Mesenchymal Igf2 is a major regulator of pancreatic growth and function

Project description:The genetic mechanisms that determine the size of the adult pancreas are not fully understood. Here we address the importance of the imprinted Igf2 gene for growth and function of the mouse pancreas. We used reporter lines to monitor Igf2 levels during late fetal and postnatal pancreatic development and demonstrate that Igf2 is mostly expressed within the mesenchyme. We manipulated Igf2 levels in vivo in the major pancreas cell types using Cre lines and found that loss of Igf2 from the developing mesenchyme results in pancreatic hypoplasia, associated with loss of acinar and beta-cell mass, postnatal whole-body growth restriction and maternal glucose intolerance during pregnancy. Overexpression of Igf2 directed to the mesenchyme results in pancreatic overgrowth. Importantly, deletion of Igf2 from the developing epithelium has no growth effects. Our findings demonstrate that a major role for Igf2 is the regulation of pancreas size, and reveal an unforeseen key function for mesenchymal IGF signalling in pancreatic growth.

2017-12-31 | GSE100981 | GEO

Transcriptional profiling of tumor-associated blood vessels in invasive bladder cancer

Project description:Tumor-associated blood vessels differ from normal vessels at the morphological and molecular level. Proteins that are only present on tumor vessels may serve as biomarkers and as therapeutic targets for inhibition of angiogenesis in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer and from normal bladder tissue, we found several markers that could serve as novel biomarkers or therapeutic targets. In this dataset, we include the expression data obtained from laser capture microdissected (LCM) vessels isolated from tumor and bladder normal tissue. 10 samples were analyzed. We compared expression of tumor associated blood vessels with expression of vessels in the normal bladder tissue using Genespring GX 12.

2013-03-08 | E-GEOD-41614 | biostudies-arrayexpress

Transcriptional profiling of tumor-associated blood vessels in invasive bladder cancer

2013-03-08 | GSE41614 | GEO

Generation of specialized blood vessels via lymphatic transdifferentiation

Project description:Generation of specialized blood vessels via lymphatic transdifferentiation

| PRJNA809307 | ENA

Bentonite clay pressure vessels

Project description:Bentonite clay pressure vessels

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Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells

Project description:We used microarrays to investigate gene expression changes in the pancreas of RasGrf1 KO mice. These animals have a reduction in the number and size of the pancreatic islets which lead to lower levels of insulin and glucagon in their blood.

2014-12-01 | GSE56371 | GEO

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