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GSE72223
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission
Publication Title
Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs), but their molecular basis is not understood. Transcription factors and Brg1/Brm-associated factor (BAF) chromatin remodeling complex interactions suggest potential mechanisms, but the role of BAF complexes in cardiogenesis is not known. Here we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20, and Nkx2-5, causes severe cardiac anomalies, revealing an essential allelic balance between Brg1 and these cardiac transcription factor genes. This suggests that relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac genes in Tbx5 haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs.
Publication Title
Chromatin remodelling complex dosage modulates transcription factor function in heart development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the developing heart, heterotypic transcription factors (TFs) interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5 have been proposed as a mechanism for human congenital heart disease. In order to study the role of each TF during heart formation, embryonic stem (ES) cell-derived embryos were generated from KO ES cells for Tbx5, Nkx2-5 or both TFs.
Publication Title
Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses.
Publication Title
Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The regulation of multipotent cardiac progenitor cell (CPC) expansion and subsequent differentiation into cardiomyocytes, smooth muscle, or endothelial cells is a fundamental aspect of basic cardiovascular biology and cardiac regenerative medicine. However, the mechanisms governing these decisions remain unclear. Here, we show that Wnt/-Catenin signaling, which promotes expansion of CPCs, is negatively regulated by Notch1-mediated control of phosphorylated -Catenin accumulation within CPCs, and that Notch1 activity in CPCs is required for their differentiation. Notch1 positively, and -Catenin negatively, regulated expression of the cardiac transcription factors, Isl1, Myocd and Smyd1. Surprisingly, disruption of Isl1, normally expressed transiently in CPCs prior to their differentiation, resulted in expansion of CPCs in vivo and in an embryonic stem (ES) cell system. Furthermore, Isl1 was required for CPC differentiation into cardiomyocyte and smooth muscle cells, but not endothelial cells. These findings reveal a regulatory network controlling CPC expansion and cell fate that involve unanticipated functions of -Catenin, Notch1 and Isl1 that may be leveraged for regenerative approaches involving CPCs.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Publication Title
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein, regulates OPC functions and remyelination in the CNS.
Publication Title
Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of early adipogenesis induced by basal adipogenesis medium(AM) and AM+Bex for 2 days in C2C12 cells
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples