This SuperSeries is composed of the SubSeries listed below.
Coassembly of REST and its cofactors at sites of gene repression in embryonic stem cells.
Cell line, Treatment
View SamplesAnalysis of gene expression profiling upon REST shRNA knockdown in mouse ES cells for 72 hours,
Coassembly of REST and its cofactors at sites of gene repression in embryonic stem cells.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transposable elements have rewired the core regulatory network of human embryonic stem cells.
Specimen part, Disease, Cell line, Time
View SamplesWe studied the genomic locations of three key regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells [see Series GSE20650]. To identify the conserved and unique human OCT4 targets, we performed an OCT4 RNAi knock-down experiment. We find that species-specific transposable elements have profoundly altered the transcriptional circuitry of pluripotent stem cells.
Transposable elements have rewired the core regulatory network of human embryonic stem cells.
Specimen part, Disease, Cell line, Time
View SamplesWe used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all.
Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium.
No sample metadata fields
View SamplesTransplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop because ECs are difficult to culture and little is known about how to sustain their vascular identity and direct them to form long-lasting new vessels or engraft into existing ones. We found that multiple non-vascular cell types transiently expressed EC markers after enforced expression of the transcription factors, Etv2, Erg, and Fli1. However, only mid-gestational amniotic cells could be converted to cells that maintained EC gene expression and proliferated in culture to yield billions of vascular cells. Even so, these converted cells performed sub-optimally in assays of EC function. We used constitutive Akt signaling to mimic the shear forces of the vascular environment and promote EC survival in an effort to correct the deficiencies of the converted cells. Akt signaling increased gene expression of EC morphogenesis genes, including Sox17, shifted the genomic targeting of Fli1 to favor nearby Sox consensus sites, and enhanced the in vivo vascular function of EC-like converted cells. Enforced expression of Sox17 was dispensable for broad EC gene activation, but indispensable for vascular engraftment and reperfusion of ischemic tissue. Our results identify a transcription factor network comprised of Ets and Sox17 factors that specifies and sustains endothelial cell fate and function. This work shows that the commonly used criterion of transcriptional similarity for cell conversion can fail to predict in vivo vascular function. Our approach shows that stringent functional testing in vitro and in vivo is necessary to validate engineered endothelial cell grafts. Overall design: Transcriptome sequencing of endothelial cells and amniotic cells
Sox17 drives functional engraftment of endothelium converted from non-vascular cells.
Specimen part, Subject
View SamplesA transcriptome-wide functional analysis of gene expression implicated multiple signaling pathways specific for Au-NP oligonucleotide complexes.
Gold nanoparticle-mediated gene delivery induces widespread changes in the expression of innate immunity genes.
Specimen part, Cell line, Treatment
View SamplesXEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm.
BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm.
Treatment
View SamplesDevelopmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. Overall design: Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
Specimen part, Subject
View SamplesComparison of mouse ES cells and three different XEN cell cultures.
Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts.
No sample metadata fields
View Samples