Unveiling the role of RAB13 localisation in angiogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio Homo sapiens
PROVIDER: GSE155449 | GEO | 2020/09/07
REPOSITORIES: GEO
Similar Datasets
Project description:Unveiling the role of RAB13 localisation in angiogenesis
| PRJNA649779 | ENA
Project description:Deciphering the complex biology of cell migration is key to understand human-related disorders. During angiogenesis, endothelial cells engage in coordinated migration events to form new blood vessels from parental counterparts. However, while subcellular localisation of mRNAs and localised translation are fundamental steps between gene transcription and protein activity, whether local regulation of gene expression controls the complex morphogenetic process of angiogenesis has never been addressed. Here, we set out to investigate the cytoplasmic distribution of mRNAs in migratory endothelial cells. We isolated RNA from endothelial cell protrusions from their cell bodies and used RNA-sequencing to identify asymmetrically distributed transcripts. These studies identified a set of transcripts enriched in endothelial cell protrusions over cell bodies, which included classically protrusion-enriched mRNAs and other intriguing transcripts encoding proteins implicated in cell migration.
2020-09-07 | GSE133055 | GEO
Project description:Most new blood vessels emerge through sprouting angiogenesis, an intricate biological process that entails the coordinated migration of groups of endothelial cells branching from parental vessels. Critical guidance cues such as the Vascular Endothelial Growth Factor secreted by the surrounding tissues regulate the molecular and cellular responses triggered during angiogenesis. Similarly to other collective cell migration systems, endothelial cells within sprouting vessels are hierarchically organised into leader tip cells and follower stalk cells. Endothelial tip cells are highly polarised, exhibiting a leading edge that extends filopodia-containing protrusions and that interacts with the extracellular matrix, whilst their rear engages in cell-to-cell contacts with stalk cells. Polarisation of cytoplasmic components contributes to dynamic membrane remodelling phenomena that are constrained to the cell-leading front during migration. Amongst other factors, asymmetric distribution of mRNA is a well-established and crucial determinant of cell polarity. The active transport of transcripts is mediated by mRNA-binding proteins (mRBPs). Subcellular distribution of transcript messages results in restricted synthesis of the proteins they encode to particular compartments within the cell. This mode of post-transcriptional control of gene expression contributes to rapid and localised cellular responses to dynamic environmental stimuli with implications in development and disease. Although the involvement of RNA interacting proteins in angiogenesis has been previously reported, whether mRBPs play a role in asymmetric transcript localisation crucial for endothelial cell migration is yet to be fully explored.
2024-03-28 | PXD046994 | Pride
Project description:Endothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor. Z/Edn2 females were crossed to Six3-Cre; Six3-Cre males. Postnatal P8 pups were genotyped for the Z/Edn2 allele by detection of Laz-Z activity in tail clips. Retinas from 2 - 3 pups were pooled for each data point.
2014-01-01 | E-GEOD-50059 | biostudies-arrayexpress
Project description:Endothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor.
2014-01-01 | GSE50059 | GEO
Project description:Regulation of subcellular mRNA localisation is a fundamental biological mechanism, which adds a spatial dimension to the diverse layers of post-transcriptional control of gene expression. Insights into this phenomenon have been described in a multitude of cell types and across taxonomic kingdoms, highlighting its biological significance. The cellular compartment in which mRNAs are located may define distinct aspects of the encoded proteins, ranging from production rate and complex formation to localised activity. Ultimately, mRNA localisation supports compartmentalised mechanistic outputs that can respond to local stimuli, orient migration, or even shape cells. We used an unbiased method to profile the RNA-bound proteome in migrating endothelial cells and found that the plasma membrane (PM)-associated A-kinase anchor protein 12 (AKAP12) interacts with various mRNAs, including mRNAs encoding kinases with Actin remodelling activity. To identify transcripts bound by AKAP12, we carried out UV crosslinking experiments followed by RNA immunoprecipitation and high throughput sequencing. Our data offer novel insights in complex mechanisms of spatial control of gene expression.
2024-03-28 | GSE247682 | GEO
Project description:Using ChECseq, we measured the effect of histone regulator depletion on chromatin protein localisation
2023-06-29 | GSE231809 | GEO
Project description:Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling.Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.
2021-09-30 | GSE161310 | GEO
Project description:Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling.Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.
2021-09-30 | GSE161236 | GEO
Project description:Existing methods to analyse RNA localisation are constrained to specific RNAs or subcellular niches, precluding the cell-wide mapping of RNA. We present Localisation of RNA (LoRNA), which maps, at once, RNAs to membranous (nucleus, ER and mitochondria) and membraneless compartments (cytosol, nucleolus and phase-separated granules). Simultaneous interrogation of all RNA locations allows the system-wide quantification of RNA proportional distribution and the comprehensive analysis of RNA subcellular dynamics. Moreover, we have re-engineered the LOPIT (Localisation Of Proteins by Isotope Tagging) method, enabling integration with LoRNA, to jointly map RNA and protein subcellular localisation. Applying this framework, we obtain a global re-localisation map for 31839 transcripts and 5314 proteins during the unfolded protein response, uncovering that ER-localised transcripts are more efficiently recruited to stress granules than cytosolic RNAs, and revealing eIF3d is key to sustain cytoskeletal function. Overall, we provide the most exhaustive map to date of RNA and protein subcellular dynamics.
2022-01-25 | PXD030456 | Pride