Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-43197
PROVIDER: PRJNA184889 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Natural cardiogenesis-based template predicts cardiogenic potential of induced pluripotent stem cell lines
2015-07-10 | E-GEOD-43197 | ExpressionAtlas
Project description:Rationale: Cardiac development is a complex process that results in the first integrated, multi-lineage embryonic tissue. Imperfect developmental progression leads to congenital heart disease, the most common birth defect with developmental corruption affecting more than 1% of all live births. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet a comprehensive transcriptome derived from natural cardiogenesis is required to establish an unbiased roadmap to gauge innate developmental milestones necessary for stem cell-based differentiation and in vitro disease modeling. Objective: Establish a contextual expression database of spatial-temporal cardiac structures, and validate a predictive tool to diagnose and predict cardiogenic outcomes from individual pluripotent stem cell lines. Methods and Results: Stage-specific cardiac structures were dissected from eight distinctive embryonic time points to produce a genome-wide expressome analysis across the spectrum of early to late cardiogenesis. Hierarchical clustering of the time course dataset demonstrated discrete gene expression profiles during natural embryonic development. In reference to the native cardiogenic expression roadmap, disruptive iPSC-derived cardiac expression profiles were revealed from pro-cardiogenic 3-factor (SOX2, OCT4, KLF4) compared to non-cardiogenic 4-factor (addition of c-MYC) reprogramming regimens upon stage-specific differentiation. Expression of cardiac-related genes from 3F-iPSC differentiated in vitro at day 0, 5, and 11 recapitulated expression of natural embryos at days 0, E7.5-E8.5, and E14.5-E18.5, respectively. In contrast, 4F-iPSC demonstrated variable gastrulation gene expression profiles beginning at day 5 of differentiation. Differential gene expression within the pluripotent ground state between the archetypical high cardiogenic potential of embryonic stem cells recapitulated in 3F-iPSC vs. the low cardiogenic potential of 4F-iPSC revealed 23 distinguishing candidate genes. Upon subsequent differentiation, cell line-specific gene expression differences were magnified to 399 genes at day 5 and 726 genes at day 11. A confirmed panel of 20 genes, differentially expressed between high and low cardiogenic cell lines, was transformed into a predictive score that was sufficient to correctly rank independent iPSC lines according to cardiogenic potential. Conclusions: Transcriptome analysis attuned to the embryonic developing heart provides a robust platform to probe coordinated cardiac specification and maturation from stem cell-based cardiogenesis model systems. Based on this genome-wide expressome roadmap, a panel of pre-cardiac genes was extracted that allowed differential prognosis of cardiogenic competency from individual reprogrammed cell lines at the pluripotent state. The overall experimental design includes 3 time points (Day0, Day5, Day11) and 3 different stem cell lines: R1 embryonic stem cells (ESCs), H9 induced pluripotent stem cells (H9-iPSCs) generated/reprogrammed by 3 transcription factors (called 3F-iPSCs), and 19BL induced pluripotent stem cells (19BL-iPSCs) generated/reprogrammed by 4 transcription factors (called 4F-iPSC). At each time point, each cell line has 3 biological replicates. In total, there are 27 samples. R1-embryonic stem cells (R1-ESCs): Day0 undifferentiated ESCs - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates. 3F-iPSC (H9 iPSCs): Day 0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates. 4F-iPSC (19BL-iPSCs): Day0 undifferentiated - 3 biological replicates, Differentiated for 5 days (Day5) - 3 biological replicates, Differentiated for 11 days (Day11) - 3 biological replicates.
2013-09-23 | E-GEOD-43197 | biostudies-arrayexpress
Project description:Rationale: Cardiac development is a complex process that results in the first integrated, multi-lineage embryonic tissue. Imperfect developmental progression leads to congenital heart disease, the most common birth defect with developmental corruption affecting more than 1% of all live births. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet a comprehensive transcriptome derived from natural cardiogenesis is required to establish an unbiased roadmap to gauge innate developmental milestones necessary for stem cell-based differentiation and in vitro disease modeling. Objective: Apply the contextual expression database of spatial-temporal cardiac structures (published in another manuscript by Li X. from the same group) to diagnose and predict cardiogenic outcomes from individual pluripotent stem cell lines. Methods and Results: Stage-specific cardiac structures were dissected from eight distinctive embryonic time points to produce a genome-wide expressome analysis across the spectrum of early to late cardiogenesis. Hierarchical clustering of the time course dataset demonstrated discrete gene expression profiles during natural embryonic development. In reference to the native cardiogenic expression roadmap, disruptive iPSC-derived cardiac expression profiles were revealed from pro-cardiogenic 3-factor (SOX2, OCT4, KLF4) compared to non-cardiogenic 4-factor (addition of c-MYC) reprogramming regimens upon stage-specific differentiation. Expression of cardiac-related genes from 3F-iPSC differentiated in vitro at day 0, 5, and 11 recapitulated expression of natural embryos at days 0, E7.5-E8.5, and E14.5-E18.5, respectively. In contrast, 4F-iPSC demonstrated variable gastrulation gene expression profiles beginning at day 5 of differentiation. Differential gene expression within the pluripotent ground state between the archetypical high cardiogenic potential of embryonic stem cells recapitulated in 3F-iPSC vs. the low cardiogenic potential of 4F-iPSC revealed 23 distinguishing candidate genes. Upon subsequent differentiation, cell line-specific gene expression differences were magnified to 399 genes at day 5 and 726 genes at day 11. A confirmed panel of 20 genes, differentially expressed between high and low cardiogenic cell lines, was transformed into a predictive score that was sufficient to correctly rank independent iPSC lines according to cardiogenic potential. Conclusions: Transcriptome analysis attuned to the embryonic developing heart provides a robust platform to probe coordinated cardiac specification and maturation from stem cell-based cardiogenesis model systems. Based on this genome-wide expressome roadmap, a panel of pre-cardiac genes was extracted that allowed differential prognosis of cardiogenic competency from individual reprogrammed cell lines at the pluripotent state.
2013-09-23 | GSE43197 | GEO
Project description:Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, the transcriptional landscape of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide expression profile of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, prioritized stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling the bioinformatics of the congenital heart disease interactome, we deconstructed disease-centric regulatory networks encoded within this cardiogenic atlas to reveal stage-specific developmental disturbances clustered on epithelial-to-mesenchymal transition (EMT), BMP regulation, NF-AT signaling, TGFb-dependent induction, and Notch signaling. Therefore, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease.
2014-05-19 | GSE51483 | GEO
Project description:Mammalian heart development is built on highly conserved molecular mechanisms with polygenetic perturbations resulting in a spectrum of congenital heart diseases (CHD). However, the transcriptional landscape of cardiogenic ontogeny that regulates proper cardiogenesis remains largely based on candidate-gene approaches. Herein, we designed a time-course transcriptome analysis to investigate the genome-wide expression profile of innate murine cardiogenesis ranging from embryonic stem cells to adult cardiac structures. This comprehensive analysis generated temporal and spatial expression profiles, prioritized stage-specific gene functions, and mapped the dynamic transcriptome of cardiogenesis to curated pathways. Reconciling the bioinformatics of the congenital heart disease interactome, we deconstructed disease-centric regulatory networks encoded within this cardiogenic atlas to reveal stage-specific developmental disturbances clustered on epithelial-to-mesenchymal transition (EMT), BMP regulation, NF-AT signaling, TGFb-dependent induction, and Notch signaling. Therefore, this cardiogenic transcriptional landscape defines the time-dependent expression of cardiac ontogeny and prioritizes regulatory networks at the interface between health and disease. To interrogate the temporal and spatial expression profiles across the entire genome during mammalian heart development, we designed a time-course microarray experiment using the mouse model at defined stages of cardiogenesis, starting with embryonic stem cells (ESC, R1 stem cell line), early embryonic developmental stages: E7.5 whole embryos, E8.5 heart tubes, left and right ventricle tissues at E9.5, E12.5, E14.5, E18.5 to 3 days after birth (D3) and adult heart (Figure 1A). At each time point, microarray experiments were performed on triplicate biological samples. Starting at E9.5, tissue samples from left ventricles (LV) and right ventricles (RV) were microdissected for RNA purification and microarray analysis to determine spatially differential gene expression between LV and RV during heart development.
2014-05-19 | E-GEOD-51483 | biostudies-arrayexpress
Project description:Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective: To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner. Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. We report the identification of putative YY1 target genes in cardiac progenitor cells (CPCs). Two samples of independently FACS-purified eGFP+ CPCs were examined against the input.
2013-06-01 | E-GEOD-35370 | biostudies-arrayexpress
Project description:Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). Objective: To identify novel regulators of mesodermal cardiac lineage commitment. Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner. Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes.
2013-06-01 | GSE35370 | GEO
Project description:<p>Variability in induced pluripotent stem cell (iPSC) lines remains a roadblock for disease modeling and regenerative medicine. Through linear mixed models we have described different sources of gene expression variability from RNA sequencing data in 317 human iPSC lines from 101 individuals. We found that ~50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele specific expression show that iPSCs retain a subject-specific gene expression pattern. Pathway enrichment and key driver analyses, based on predictive causal gene networks, found that Polycomb targets explain a significant part of the non-genetic variability present in iPSCs within and across individuals. These publically available iPSC lines and genetic datasets will be a resource to the scientific community and will open new avenues to reduce variability in iPSCs and improve their utility in disease modeling.</p> <p>SNP array data from individuals included in RNA-seq transcriptome profiling study of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual. Genotyping was performed on patient blood.</p> Data availability: <ul> <li>SNP-genotyping: dbGaP - current study</li> <li>RNA-seq counts: <a href="http://www.ncbi.nlm.nih.gov/geo/">GEO</a> - GSE79636</li> <li>FASTQ files: <a href="http://www.ncbi.nlm.nih.gov/sra">SRA</a> - SRP072417</li> </ul>
| phs001139 | dbGaP
Project description:Here we extend our previous EMLO gastruloid technology to cardiac (EMLOC) with the generation of interconnected neuro-gut-cardiac interconnected multilineages. The contractile EMLOCs recapitulate numerous developmental features of heart tube formation and specialization, cardiomyocyte differentiation and remodeling phases, epicardium, ventricular wall morphogenesis, and formation of the putative outflow tract. Cardiogenesis in EMLOCs originates anterior to the gut tube primordium and we observe neurons that progressively populate the cardiogenic region in a pattern that mirrors the spatial distribution of neurons in heart innervation. The EMLOC mode represents the first multi-lineage advancement of neuro-cardiac lineages in a gastruloid model that parallels human cardiogenesis with neurogenesis.
2022-05-06 | GSE194356 | GEO
Project description:Endothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl-/- embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31+Pdgfrα+ cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl-/- hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Sclfl/flRosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl-/- endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.
2012-08-03 | GSE27445 | GEO