Transcriptomic analysis in E9.5 heart tubes identify genes dysregulated in Sox7-null heart tubes
Ontology highlight
ABSTRACT: RNA-seq differential gene expression analysis was accomplished in E9.5 pooled(n = approximately 30) microdissected heart tubes from Sox7-null embryos and a wild-type littermates.
Project description:To identify genes that are differentially expressed in the developing mouse embryo as a result of SOX7 deficiency, we performed bulk RNA-seq on Sox7-null and wild-type embryos harvested at E8.5.
Project description:Presomitic mesoderm (PSM) were microdissected from E9.5 mouse embryos (WT and TCre/+;Taf10flox/flox). 3 PSM (17-19 somites stage) were pooled per microarray, in triplicates, per genotypes
Project description:Specification of the mesodermal lineages requires a complex set of morphogenetic events orchestrated by interconnected signaling pathways and gene regulatory networks. The transcription factor Sox7 has critical functions in differentiation of multiple mesodermal lineages, including cardiac, endothelial, and hematopoietic. Using a doxycycline-inducible mouse embryonic stem cell (mESC) line, we have previously shown that expression of Sox7 in cardiovascular progenitor cells promotes expansion of endothelial progenitor cells. Here, we show that the ability of Sox7 to promote endothelial cell fate occurs at the expense of the cardiac lineage. Using ChIP-Seq coupled with ATAC-Seq we identify downstream target genes of Sox7 in cardiovascular progenitor cells and, by integrating these data with transcriptomic analyses, we define Sox7-dependent gene programs specific to cardiac and endothelial progenitor cells. Further, we demonstrate a protein-protein interaction between SOX7 and GATA4 and provide evidence that Sox7 interferes with the transcriptional activity of Gata4 on cardiac genes. In addition, we show Sox7 modulates WNT and BMP signaling during cardiovascular differentiation. Our data represent the first genome-wide analysis of Sox7 function and reveal a critical role for Sox7 in regulating signaling pathways that affect cardiovascular progenitor cell differentiation.
Project description:Lamin B1 ChIP-seq analysis of microdissected whole hearts from E9.5 and E12.5 CD1 embryos. Results provide insight into in vivo genome-nuclear lamina interactions over the course of embryonic development. Progenitor cells require coordinated expression of lineage-specific genes to regulate differentiation into daughter cell types. Epigenetic regulators are ideally positioned to synchronize transcription of disparate genomic loci. Using cardiac development to model progenitor cell behavior, we map genome- lamina interactions in vivo to reveal dynamic changes during cardiac development and propose that Hdac3 mediates chromatin organization and gene positioning in cardiac progenitors to regulate fate decisions.
Project description:To understand the role of Sox7 in primitive endoderm differentiation, we compare the gene expression pattern of Sox7 (+/-) and Sox7 (-/-) ES cells with or without dexamethasome (Dex) treatment. Because these ES cells harbour Gata6-GR transgene, Dex treatment forces ES cells differentate into XEN-like cells. As Sox7 (-/-) ES cells can differentiate into XEN-like cell by morphology, we assessed genome wide gene expression pattern.
Project description:As a transcription factor, SOX7 suppresses cancer development. However, only a few genes were demonstrated as SOX7-activated targets in cancer-irrelevant contexts. We used microarray chips to determine SOX7 target genes in breast cancer cells and discovered multiple signaling pathways altered by ectopic SOX7. We also investigated several genes for their roles in SOX7-mediated tumor suppression. Our study innovatively revealed SOX7 target gene profile in a cancer-relevant context and identified several SOX7-repressed target genes.
Project description:We investigated SOX7 binding events on the chromatin under basal conditions in human umbilical vein endothelial cells, upon overexpression of human SOX7-mCherry and immunoprecipitating mCherry. Cells overexpressing only the mCherry tag were used as negative control condition, and peaks called here were substracted from the SOX7-mCherry peaks.