Endothelial progenitor migration and differentiation is regulated by distinct transcriptional effectors of Cloche/Npas4l
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ABSTRACT:
PROVIDER: PRJNA700672 | ENA |
REPOSITORIES: ENA
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Project description:Embryonic cells including endothelial progenitors undergo extensive migration and differentiation events; however, whether and how these processes are interrelated remains unclear. The transcription factor Npas4l is necessary for endothelial specification in zebrafish by inducing the expression of the transcription factor genes etsrp, tal1 and lmo2. We generated a knock-in reporter in the npas4l locus to visualize endothelial progenitors and their derivatives in wild-type and mutant embryos. We find that in npas4l mutants, npas4l reporter expressing cells do not migrate to the midline and instead contribute to skeletal muscle and pronephric tubules. Investigating the Npas4l transcriptional effectors, we find that npas4l reporter expressing cells in tal1 mutants fail to migrate while those in etsrp mutants migrate but fail to differentiate. In lmo2 mutants, npas4l reporter expressing cells migrate and differentiate, but many express pronephric tubule markers. Altogether, these data reveal the complex regulation of endothelial progenitor migration, differentiation and fate restriction.
2022-07-11 | GSE166396 | GEO
Project description:Microarray analysis of triplicate RNA samples isolated from kdrl:eGFP-sorted ECs of wildtype, npas4l-/-, etsrp-/-, and sox32-/- zebrafish embryos in Tg(kdrl:EGFP) transgenic background between 18 and 18.5 hpf.
2020-10-20 | E-MTAB-9698 | biostudies-arrayexpress
Project description:The endocardium plays important roles in the development and function of the vertebrate heart; however, few molecular markers of this tissue have been identified and little is known about what regulates its differentiation. Here, we describe the Gt(SAGFF27C); Tg(4xUAS:egfp) line as a marker of endocardial development in zebrafish. Transcriptomic comparison between endocardium and pan-endothelium confirms molecular distinction between these populations and time-course analysis suggests differentiation as early as eight somites. To investigate what regulates endocardial identity, we employed npas4l, etv2 and scl loss-of-function models. Endocardial expression is lost in npas4l mutants, significantly reduced in etv2 mutants and only modestly affected upon scl loss-of-function. Bmp signalling was also examined: overactivation of Bmp signalling increased endocardial expression, whereas Bmp inhibition decreased expression. Finally, epistasis experiments showed that overactivation of Bmp signalling was incapable of restoring endocardial expression in etv2 mutants. By contrast, overexpression of either npas4l or etv2 was sufficient to rescue endocardial expression upon Bmp inhibition. Together, these results describe the differentiation of the endocardium, distinct from vasculature, and place npas4l and etv2 downstream of Bmp signalling in regulating its differentiation.
2022-05-01 | GSE201611 | GEO
Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
2019-05-21 | GSE130196 | GEO
Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
2019-05-21 | GSE130198 | GEO
Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
2019-05-21 | GSE130200 | GEO
Project description:The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification in vertebrates remains incomplete. cloche/npas4l mutants have broadly been used as an avascular model in zebrafish, but little is known about the molecular mechanism of action of Npas4l. Here, to identify the direct and indirect target genes of this transcription factor, we combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation (ChIP). The cross-analysis of these datasets indicate that Npas4l functions as a master regulator by directly inducing a wave of transcription factor genes crucial for hematoendothelial specification in vertebrates, including etv2, tal1, and lmo2. We identified additional target genes acting downstream of npas4l and investigated the function of a subset of them using CRISPR/Cas9 technology. Phenotypic characterization of tspan18b mutants reveals a novel role for tspan18b in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to investigate novel genes with a potential role in vascular development and EC fate determination in vertebrates.
2019-05-21 | GSE130199 | GEO
Project description:Legionella pneumophila is a Gram-negative, environmental bacterium, which causes the life-threatening pneumonia Legionnaires’ disease. The facultative intracellular bacterium forms biofilms and employs the Icm/Dot type IV secretion system (T4SS) to replicate in amoebae and macrophages. The Legionella quorum sensing (Lqs) system and the transcription factor LvbR form a regulatory network controlling various traits, including bacterial motility, virulence and biofilm architecture. Here we show by comparative proteomics that in biofilms formed by L. pneumophila mutant strains lacking LvbR or the response regulator LqsR, proteins encoded by the 133 kb fitness island and components of the flagellum (FlaA) are downregulated. Confocal microscopy revealed that the ∆lqsR or ∆flaA mutant strains formed biofilms of the same patchy morphology as the parental strain JR32, while the ∆lvbR mutant forms a mat-like biofilm as previously shown. Acanthamoeba castellanii amoebae migrated more slowly through biofilms formed by the ∆lvbR, ∆lqsR or ∆flaA mutant strains, and amoebae migration was impaired in biofilms formed by L. pneumophila lacking a functional Icm/Dot T4SS (∆icmT) or the secreted effector proteins LegG1 and PpgA. Amoebae migrating through biofilms formed by JR32, ∆lvbR or ∆icmT were decorated by clusters of bacteria, while amoebae in ∆lqsR or ∆flaA biofilms were not. Taken together, the Lqs system, LvbR, FlaA and the Icm/Dot T4SS regulate migration of A. castellanii through L. pneumophila biofilms, and – with the exception of the T4SS – also regulate bacterial cluster formation on the amoeba. Hence, amoebae migration through L. pneumophila biofilms is regulated by bacterial quorum sensing, virulence and motility.
2022-06-08 | PXD030337 | Pride
Project description:Colorectal cancer (CRC) is one of the common malignancies worldwide, accounting for a significant percentage of cancer mortality. Concurrent chemoradiation (CCRT) is now a standard treatment for unresectable malignancies of anorectum. To improve quality of life, CCRT is also commonly applied in treatment of lower rectal and anal canal cancer to preserve anal sphincter function. The most commonly used chemotherapeutic drugs combined with radiation as radiosensitizers is 5-fluorouracil (5-FU). Circulating endothelial progenitor cells (EPC), which contribute to the tumor vessel formation, reflect the response to chemotherapy both in animal model and clinical trial. Thus, circulating EPC can be used as a marker for optimizing and monitoring the anti-angiogenesis therapy including angiogenesis inhibitors and chemotherapy. Whether circulating EPC can be served as a marker of CCRT efficacy or not remains undetermined. Since CCRT is now a standard treatment of locally advanced and high-risk CRC, the development of a surrogate marker for monitoring CCRT response and optimize treatment intensity is very important.
In this grant we intent to monitor the levels of circulating EPC in locally advanced and high-risk CRC patients before, during and after CCRT. To further characterize the changes in function and biology of EPC caused by CCRT, a syngeneic animal model will be also used to evaluate the clonogenecity and specific gene expression of EPC in tumor-bearing mice receiving CCRT.
| 2028928 | ecrin-mdr-crc
Project description: Not available
| S-EPMC3238468 | biostudies-literature