Vascular endothelial cells differentiation from mouse embryonic stem cells
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ABSTRACT:
PROVIDER: PRJNA374535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5249580.fastq.gz | Fastqsanger.gz | |||
| SRR5249590.fastq.gz | Fastqsanger.gz | |||
| SRR5249581.fastq.gz | Fastqsanger.gz | |||
| SRR5249591.fastq.gz | Fastqsanger.gz | |||
| SRR5249572.fastq.gz | Fastqsanger.gz |
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Project description:Although differentiation of mice embryonic stem cells into vascular endothelial cells (ECs) gives a model for investigating molecular mechanisms of vascular development in vivo, temporal dynamics of gene expressions and chromatin modifications have not been studied until now. Here, we interrogated transcriptome and two histone modifications, H3K4me3 and H3K27me3, with a genome-wide scale during ECs differentiation and elucidated epigenetic switch peculiar to ECs. We find Gata2, Fli1, Sox7, and Sox18 are master regulators from genetic and epigenetic data, these genes were induced after Etv2 activation. These genes have specific histone modification pattern which is repressed by H3K27me3 modification at Flk-sorted mesoderm and changed to the bivalent (H3K4me3 and H3K27me3 both positive) state rapidly after vascular endothelial cells growth factor (VEGF) stimuli. Using a previously reported ECs differentiation model, we demonstrate that four transcription factors are critical for ECs specific gene expressions and efficient differentiation. Moreover, from knockdown experiments using si-RNA, we discovered these factors inhibited not only TGFβ signaling pathway, that is endothelial mesenchymal transition pathway, but also other near lineage commitment, including blood cells, skeletal muscle cells, vascular smooth muscle cells, and cardiomyocytes. We further identify each factor specific target genes during ECs differentiation by microarray, including both activating and repressing genes. Together, our findings from a detailed epigenetic approach provide a basic understanding temporal regulated chromatin signatures and resulting gene expression profile during ECs commitment, which is applicable to other models of differentiation and production of mature and long lasting ECs for regenerative medicine. Total 17 samples were derived from [1] ES cells, Flk-sorted mesoderm cells, and in the absense or presence of VEGF (6, 12, 24, and 48h) to determine VEGF activated genes during endothelial cells differentiation, [2] control si-RNA, si-Gata2, si-Fli1, si-Sox7, or si-Sox18 transfected cells under VEGF stimuli, [3] control si-RNA or si-Mix (si-Gata2, si-Fli1, si-Sox7, and si-Sox18) transfected cells under VEGF stimuli for the identification of each transcription factor dependent genes during endothelial cells differentiation.
2016-07-18 | E-GEOD-76964 | biostudies-arrayexpress
Project description:Although differentiation of mice embryonic stem cells into vascular endothelial cells (ECs) gives a model for investigating molecular mechanisms of vascular development in vivo, temporal dynamics of gene expressions and chromatin modifications have not been studied until now. Here, we interrogated transcriptome and two histone modifications, H3K4me3 and H3K27me3, with a genome-wide scale during ECs differentiation and elucidated epigenetic switch peculiar to ECs. We find Gata2, Fli1, Sox7, and Sox18 are master regulators from genetic and epigenetic data, these genes were induced after Etv2 activation. These genes have specific histone modification pattern which is repressed by H3K27me3 modification at Flk-sorted mesoderm and changed to the bivalent (H3K4me3 and H3K27me3 both positive) state rapidly after vascular endothelial cells growth factor (VEGF) stimuli. Using a previously reported ECs differentiation model, we demonstrate that four transcription factors are critical for ECs specific gene expressions and efficient differentiation. Moreover, from knockdown experiments using si-RNA, we discovered these factors inhibited not only TGFβ signaling pathway, that is endothelial mesenchymal transition pathway, but also other near lineage commitment, including blood cells, skeletal muscle cells, vascular smooth muscle cells, and cardiomyocytes. We further identify each factor specific target genes during ECs differentiation by microarray, including both activating and repressing genes. Together, our findings from a detailed epigenetic approach provide a basic understanding temporal regulated chromatin signatures and resulting gene expression profile during ECs commitment, which is applicable to other models of differentiation and production of mature and long lasting ECs for regenerative medicine.
2016-07-18 | GSE76964 | GEO
Project description:Although studies of the differentiation from mouse embryonic stem (ES) cells to vascular endothelial cells (ECs) provide an excellent model for investigating the molecular mechanisms underlying vascular development, temporal dynamics of gene expression and chromatin modifications have not been well studied. Herein, using transcriptomic and epigenomic analyses based on the H3K4me3 and H3K27me3 modifications at a genome-wide scale, we analyzed the EC differentiation steps from ES cells and crucial epigenetic modifications unique to ECs. We determined that Gata2, Fli1, Sox7, and Sox18 are master regulators of EC induced following expression of the hemangioblast commitment pioneer factor, Etv2. These master regulator gene loci were repressed by H3K27me3 under the mesoderm period, but rapidly transitioned to the histone modification switching from H3K27me3 to H3K4me3 after treatment with vascular endothelial growth factor (VEGF). SiRNA knockdown experiments indicated that these regulators are indispensable not only for proper EC differentiation but also for blocking the commitment to other closely aligned lineages. Collectively, our detailed epigenetic analysis might provide an advanced model for understanding temporal regulation of chromatin signature and resulting gene expression profiles during EC commitment. These studies would lead the future development of methods to amplify the vascular endothelium for regenerative medicine.
2017-02-13 | GSE94828 | GEO
Project description:Morphogenesis and differentiation of embryonic vascular smooth muscle cells in zebrafish
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Project description:Endothelial differentiation occurs during normal vascular development in the developing embryo. Mouse embryonic stem (ES) cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2 + cells, that were CD41+ positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin) was also identified at this same time point. Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2, CD41, and CD144. Keywords: expression analysis
2008-07-14 | GSE10210 | GEO
Project description:Endothelial differentiation occurs during normal vascular development in the developing embryo. Mouse embryonic stem (ES) cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2 + cells, that were CD41+ positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin) was also identified at this same time point. Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2, CD41, and CD144. Experiment Overall Design: We identified four populations of cells; cells expressing VEGF-R2 (day 2.5), CD41 expressing cells (day 3.5), cells expressing CD144 (VE-Cadherin, day 3.5), and cells expressing CD144 (day 6.5). In addition to this, we have also obtained the negative control cells at each time such as VEGF-R2 (day 2.5) negative, CD41 negative (day 3.5), CD144 negative (VE-Cadherin, day 3.5), and negative CD144 (day 6.5). RNA for the microarray experiments were obtained in duplicate from two separately conducted experiments using the murine embryonic stem cells..
2008-10-20 | E-GEOD-10210 | biostudies-arrayexpress
Project description:Angiogenesis and lymphangiogenesis have important roles in cancer progression and chronic inflammatory diseases, but efficient therapies against these diseases have been hampered by the lack of identified vascular lineage-specific markers and growth factors. Using transcriptional profiling of matched pairs of human dermal blood vascular and lymphatic endothelial cells, we first identified 236 lymphatic and 342 blood vascular signature genes. In silico analyses of the biologic pathways associated with these genes revealed lineage-specific functions for each cell type. Using a selection of 85 identified vascular lineage-specific genes, we developed a TaqMan RT-PCR-based, microfluidic card-formatted low-density microvascular differentiation array (LD-MDA) that was used to reliably identify and quantify the degree of lineage-specific differentiation in different types of endothelial cells, and to detect admixture of lymphatic endothelial cells in commercial preparations of microvascular endothelial cells. Application of Prediction Relevance Ranking and analysis of variance of LD-MDA expression profiles of 43 lesional skin samples obtained from patients with the chronic inflammatory disease psoriasis led to identification of cytokines which are significantly associated with angiogenesis or lymphangiogenesis in vivo. In particular, interleukin-7 and fibroblast growth factor-12 were identified as novel (lymph)angiogenic factors. This technology provides a novel tool to quantify lineage-specific vascular differentiation and to characterize (lymph)angiogenesis in clinical samples obtained from angiogenic diseases. This SuperSeries is composed of the following subset Series: GSE11306: Quantification of vascular lineage-specific differentiation (cell type comparison) GSE11307: Quantification of vascular lineage-specific differentiation, psoriasis (chronic inflammation) study Keywords: SuperSeries Refer to individual Series
2008-10-04 | E-GEOD-11308 | biostudies-arrayexpress
Project description:Transcriptome analysis of human embryonic stem cell differentiation to endothelial cells
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Project description:We previously reported that a vascular endothelial stem cell population resides in pre-existing blood vessels in mice and may contribute to vascular endothelial cells in liver injury or hind limb ischemia models in the long-term. However, whether such stem cells exist in humans and can differentiate specifically into vascular endothelial cells have not been determined. We hypothesized that CD157+ vascular endothelial cells in humans may also possess high angiogenic potential. First, human-derived induced pluripotent stem cells were differentiated into vascular endothelial cells, and the expression of CD157 was monitored during the differentiation process. We found that CD157 emerged 11 days after the induction of differentiation, peaked at 14 days, and then declined by 24 days. WNext, we also evaluated blood vessel formation by 14- and 24-day-old vascular endothelial cells.It was found that 14-day-old cells, when CD157 expression was at its peak, formed more blood vessels than 24-day-old cells.These results suggest that vascular endothelial cells expressing CD157 have high angiogenic potential and may exist as vascular endothelial stem cells.
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