E-MTAB-4578
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-4578 | ExpressionAtlas | 2019-05-14
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The post-implantation embryo is subject to extensive growth, morphogenetic changes and lineage decisions that take place in utero and are therefore difficult to deconstruct in vivo. A robust in vitro culture system that mimics post-implantation mouse development would pave the path towards understanding the dynamics of these processes and how they are coupled. Small aggregates of mouse embryonic stem cells (mESCs) can undergo gastrulation-like events and elongation in vitro, resulting in aggregates with gene expression domains that reflect the post-occipital embryo (gastruloids1–3). However, these ordered patterns of gene expression do not correlate with embryo-like morphogenesis. Here we show that mechano-chemical manipulation of the aggregates results in Trunk-Like-Structures (TLS) with a high level of organization of the embryonic tissue layers, including the formation of a neural tube and somites. Comparative single-cell RNA-Seq (scRNA-Seq) of TLS and embryos demonstrated the molecular complexity of TLS, confirmed embryo-like gene-regulatory programs, and unveiled the presence of primordial germ cell like cells (PGCLCs). Finally, Tbx6-/- TLS formed ectopic neural tubes, recapitulating the in vivo phenotype. These results suggest that TLS are a powerful platform to study the morphogenetic changes and lineage decisions during post-implantation development in space and time.
2020-12-14 | GSE141175 | GEO
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
2021-07-01 | MODEL2105030001 | BioModels
Project description:Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determined, for the first time, the global lineage-specific lncRNAome of human dermal blood and lymphatic endothelial cells (BECs and LECs), combining RNA-Seq and CAGE-Seq. A subsequent genome-wide antisense oligonucleotide-knockdown profiling of two BEC- and two LEC-specific lncRNAs identified LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA and RNA-protein interaction studies, and phenotype rescue analyses revealed that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes governing the growth and migratory ability of LECs. Together, our study provides new evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.
2020-12-21 | PXD018578 | Pride
Project description:<p>In this study, we describe a systematic analysis of pseudogene 'transcription' from an RNA-Seq resource of 293 samples, from 13 cancer and normal tissue types. We observed a highly prevalent, genome-wide expression of pseudogenes that could be categorized as universally expressed or lineage- and/or cancer-specific. We also explored disease subtype specificity and functions of selected expressed pseudogenes. We provide evidence that transcribed pseudogenes are a significant contributor to the transcriptional landscape of cells and are positioned to play significant roles in cellular differentiation and cancer progression. Our work provides a transcriptome resource that enables high-throughput analyses of pseudogene expression.</p>
| phs000525 | dbGaP
Project description:The blueprint of lineage segregation of early mouse embryo is established during gastrulation in which progenitors of various cell fates are regionalized and patterned in specific embryo locations. Despite the central importance of this period of mammalian development, we currently lack a comprehensive understanding of the underlying developmental trajectories and molecular processes, principally because research efforts either employed in vitro systems, focused on small numbers of genes, or limited the number of developmental stages or cell types that were studied. Here, we study the regulatory landscape of gastrulation by combining single-cell RNA-seq (A total of ~35,000 single cells isolated at E6.5, E6.75, E7.0, E7.25, E7.5) and geographical position sequencing (Geo-seq) technique, and we report a de novo identification of spatial signatures and a method to enable retrospective locating of single cells to their origins. Our work provides insights into the exit from pluripotency and priming for differentiation, and the emergence of regulatory networks associated with cell fate decisions. Finally, we reconstruct the spatio-temporal roadmap of gastrula mouse embryo in single-cell resolution. This result uncovers the cell migration trajectories and molecular processes associated with lineage segregation.
2023-08-15 | GSE171588 | GEO
Project description:whole genome sequencing data of parent blood samples. Single cell full-length RNA-seq and PBAT-Seq data of in vitro culture D6 to D14 human embryo.
| EGAD00001005137 | EGA
Project description:Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extra-embryonic lineages of the post-implantation embryo by transcription factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation, and formation of the anterior-posterior axis, brain, a beating heart structure, and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages, but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole embryo-like structure.
2022-09-17 | E-MTAB-12140 | biostudies-arrayexpress
Project description:<p> <ol> <li>Implement an efficient, highly reproducible and 'scalable' system for the production of large numbers of sickle cell anemia-specific iPS cells (iPSC).</li> <li>Derive and characterize a novel, in vitro system for the production of an unlimited supply of erythroid lineage cells from the directed differentiation of 'clinical grade' transgene-free iPS cells; use this system to recapitulate erythroid-lineage ontogeny in vitro with the sequential development of primitive and definitive erythropoiesis, accompanied by the appropriate expression of stage-specific globin genes.</li> <li>Identify developmental gene expression profile differences between erythroid precursors that produce primarily HbF and those that produce primarily HbA or HbS.</li> <li>Determine the effects of the three known HbF major quantitative trait loci (QTL) on globin gene expression in disease-specific iPS cells during in vitro erythropoiesis.</li> <li>Search for novel HbF genetic modifiers associated with markedly elevated HbF levels found in sickle cell anemia patients naturally, or in response to hydroxyurea treatment, by examining gene expression profiles and mRNA sequence of their iPSC-derived erythroid cells.</li> <li>Develop and use a CRISPR-based gene editing platform to study the effect of novel HbF genetic modifiers, explore globin switching, and correct the HbS mutation in sickle iPSC lines.</li> </ol> </p>
| phs001212 | dbGaP
Project description:The Prep1 (Pknox1) homeodomain transcription factor is essential at multiple stages of embryo development. In the E11.5 embryo trunk, we previously estimated that Prep1 binds about 3,300 genomic sites at a highly specific decameric consensus sequence, mainly governing basal cellular functions. We now show that in embryonic stem (ES) cells Prep1 binding pattern only partly overlaps that of the embryo trunk, with about 2,000 novel sites, highlighting a change of targets between embryonic differentiated v. embryonic stem cells. RNA-seq identifies about 1800 genes down-regulated in Prep1- /- ES cells which belong to gene ontology categories not enriched in the E11.5 Prep1i/i differentiated embryo, including in particular the Wnt and Fgf pathways. Indeed, we find aberrant Wnt and Fgf expression levels in the Prep1-/- ES cells which agrees with a deficient embryoid bodies (EBs) differentiation. Re-establishment of the Prep1 level rescues the phenotype. [ChIP-Seq] Examination of genome-wide Prep1 binding in mouse ES cells using ChIP-seq and Illumina GAII sequencing. [RNA-Seq] Examination of gene expression in wild type and Prep1-/- mouse ES cells using RNA-seq and Illumina GAII sequencing.
2015-04-01 | E-GEOD-63282 | biostudies-arrayexpress
Project description:The mammalian TET dioxygenases contribute to global waves of DNA demethylation in the zygote and in primordial germ cells, but their involvement during de novo DNA methylation at peri/post-implantation development is unknown. Here, we show novel physiological functions of Tet1 in the pre-primitive streak stage mouse embryo, where it is expressed not only in the primed-state epiblast, but also in the extra-embryonic ectoderm. In the epiblast, Tet1 contributes to DNA methylation patterning, which indirectly results in dominant transcriptional repression involving a Jumonji-family gene Jmjd8. In the extra-embryonic ectoderm, Tet1 suppresses expression of metabolic genes involved in oxidative phosphorylation. These lineage-specific gene repressive functions, involving distinct modes of regulation by DNA methylation, counteract precocious differentiation of the embryo prior to the onset of gastrulation. Such dysregulation in the absence of Tet1 are surprisingly tolerated in an inbred strain but results in full embryonic lethality in non-inbred mice, thus implicating a complex but essential role of Tet1 in normal gestational development.
2017-05-15 | E-MTAB-4581 | biostudies-arrayexpress