Tracking Early Mammalian Organogenesis – Prediction and Validation of Differentiation Trajectories at Whole Organism Scale
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Mus musculus
SUBMITTER: John Marioni
PROVIDER: E-MTAB-11763 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-07 | E-GEOD-62072 | biostudies-arrayexpress
Project description:Gastrulation represents a pivotal point in mammalian development, when the basic body plan is established and cells are specified into one of the three germ layers. This is followed by rapid diversification into specific lineages and the appearance of the various cell types required to build each of the organs. The rich variety of cell types present at this stage has never been rigorously characterised in any mammalian organism, and thus insight into cell fate decisions and the underlying regulatory networks have been inaccessible. We have used droplet based single-cell RNA-sequencing to address this by profiling ~20000 cells from C57BL/6 E8.25 mouse embryos.
2017-12-01 | E-MTAB-6153 | biostudies-arrayexpress
Project description:At an incidence of approximately 1/1000 births, neural tube defects (NTDs) comprise one of the most common and devastating congenital disorders. In an attempt to enhance and expand our understanding of neural tube closure, we undertook a high-throughput gene expression analysis of the neural tube as it was forming in the mouse embryo. Open and closed sections of the developing neural tube were micro-dissected from mouse embryos, and hybridized to Affymetrix mouse expression arrays. Clustering of genes differentially regulated in open and closed sections of the developing neural tube highlighted molecular processes previously recognized to be involved in neural tube closure and neurogenesis. Analysis of the genes in these categories identified potential candidates underlying neural tube closure. In addition, we identified approximately 25 novel genes, of unknown function, that were significantly up-regulated in the closed neural tube. Based on their expression patterns in the developing neural tube, five novel genes are proposed as interesting candidates for involvement in neurogenesis. The high-throughput expression analysis of the neural tube as it forms allows for better characterization of pathways involved in neural tube closure and neurogenesis, and hopefully will strengthen the foundation for further research along the pathways dictating neural tube development. Embryos were dissected at days E8.5 and E9.5, and the neuroepithelium/ neural tube were mechanically detached from underlying tissues, and then separated into two regions: 1) M-bM-^@M-^\open neuroepitheliumM-bM-^@M-^]: neuroepithelial tissue caudal to the open/closed junction, and 2) M-bM-^@M-^\closed neural tubeM-bM-^@M-^], extending from a somiteM-bM-^@M-^Ys breadth rostral to the open/closed junction, up to the level of the fifth- or sixth-to-last somite. Samples consisted of biological triplicates of RNA extract from the above tissues (pooled by litter, and representing a total of 111 embryos): E8.5 open neuroepithelium, E8.5 closed neural tube, E9.5 open neuroepithelium, and E9.5 closed neural tube. Thus, a total of 12 samples (representing 111 embryos) were hybridized to the GeneChip Mouse Genome 430 2.0 Array (Affymetrix Inc., Santa Clara, CA, USA). One of the samples (06, closed E8.5) deviated significantly from the others in quality assessment and was therefore removed from subsequent analysis and not submitted to GEO.
2014-01-01 | E-GEOD-39442 | biostudies-arrayexpress
Project description:BAF155, as a component of a chromatin remodeling complex, is thought to be involved in the regulation of gene expression. Baf155 knockdown in ES cells results in misregulation of hundreds of genes (Ho et al., 2009). The Baf155msp3 allele presents a unique case for gene expression analysis wherein the BAF complex appears to be intact, in contrast to disruption of the BAF complex when BAF155 function is lost (Chen and Archer, 2005; Sohn et al., 2007). To examine gene expression in the Baf155msp3 mutant at the time of neural tube closure, we performed RNA-Seq and compared gene expression levels between homozygous wildtype and homozygous mutant embryos. After extensive analysis of the RNA-Seq data comparing all 3 mutants to all 3 WT replicates, 78 genes were identified as being upregulated on average in the mutant samples while 22 genes were downregulated. To facilitate an understanding of global gene expression differences, Ingenuity Pathway Analysis (IPA) was used to assign functional categories to the up- and down-regulated genes in the mutants. The most significant molecular and cellular functions of these genes were: 1. cellular movement (1.46E-04>p>4.12E-02), 2. cell death and survival (2.69E-04>p>4.12E-02), and 3. cell growth and proliferation (2.69E-04>p>3.41E-02). Many neuronal genes were significantly misregulated as well. Overall, the RNA-Seq analysis revealed that surprisingly few genes showed altered expression in Baf155 mutant neural tissue, given the broad epigenetic role of the BAF complex, but included genes involved in neural development and cell survival. Moreover, gene expression changes between individual mutants were variable even though the NTD was consistently observed. This suggests that inconsistent gene regulation contributes to failed neural tube closure. RNA was isolated from somite matched (21-23 somites) and phenotype matched cranial tissue of homozygous wildtype and homozygous mutant embryos (3 of each genotype) at E9.5 just after the time of neural tube closure. At E9.5, the vast majority of the embryonic neural tube is comprised of proliferating neural progenitor cells, constituting a relatively homogeneous cell population.
2014-01-31 | E-GEOD-53459 | biostudies-arrayexpress
Project description:Gene expression profiles were compared between wild-type and Jmjd3-/- embryos at E9.5 when mRNAs of posterior Hox genes are upregulated, because Jmjd3-/- mice embryos showed homeotic transformation. As expected, mRNAs of Hoxd10 and Hod11 were decreased in Jmjd3-/- embryos. Moreover, gene onthology (GO) analyses identified down-regulated genes (FC>1.5) in Jmjd3-/- embryos were M-bM-^@M-^\multicellular organismal developmentM-bM-^@M-^] and M-bM-^@M-^\developmental processM-bM-^@M-^]. Gene expressions in wild-type and Jmjd3-/- posterior half of embryos at E9.5 were examined. Two independent RNA samples of each genotypes were used to verify the reproducibility of the microarray analyses.
2014-02-23 | E-GEOD-40332 | biostudies-arrayexpress
Project description:As Sox17 plays a critical role in the development of multiple cell types during early embryogenesis, we utilized a dual-color lineage-tracing strategy in combination with single-cell RNA sequencing (scRNAseq) to capture and analyze Sox17-expressing lineages. GFP production from Sox17GFPCre allele marks cells that currently express Sox17 or short-term progeny of Sox17 expressing progenitors. TdTomato production from R26LSL.TdTomato reporter allele in the presence of Sox17GFPCre marks long-term progeny of Sox17-expressing progenitors. In brief, GFP and Tdtomato positive cells were isolated from E9.5 embryos of specific genotypes to generate two separate scRNAseq datasets, referred to in the manuscript as the GFP and TdTomato datasets, respectively.
2023-07-20 | E-MTAB-12719 | biostudies-arrayexpress
Project description:The study sought to determine whether deletion of individual seed families within the miR-17~92 cluster affected the expression of the remaining microRNAs of the cluster. There were 8 samples analyzed. The reference is the wild-type embryo.
2015-05-22 | E-GEOD-63660 | biostudies-arrayexpress
Project description:The Deciphering the Mechanisms of Developmental Disorders (DMDD) programme analyses the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines. Here we show that single whole embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) uncovers transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. Further, we separate embryonic delay signatures from line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during somitogenesis. Collectively, this work provides a rich resource to further our understanding of early embryonic developmental disorders.
2019-10-31 | E-MTAB-7322 | biostudies-arrayexpress
Project description:To determine the role of specific cis-regulatory elements within the Sox17 endoderm-preferential TSS2 promoter, we generated Sox17∆50 mutant animals and surveyed how this mutation altered Sox17 expression. Livers were isolated from E12.5 Sox17∆50/∆50 and Sox17+/+ embryos (n = 4 of each genotype), RNA isolated, and bulk RNA-Seq performed.
2024-10-31 | E-MTAB-13982 | biostudies-arrayexpress