Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360989 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The spinal cord and mesodermal tissues of the trunk such as the vertebral column and skeletal musculature derive from neuro-mesodermal progenitors (NMPs). Sox2, Brachyury (T) and Tbx6 have been correlated with NMP potency and lineage choice, however, their exact role and interaction in these processes have not been revealed yet. Here we present a global analysis of NMPs and their descending lineages performed on purified cells from E8.5 wild-type and mutant embryos. We show that T, cooperatively with WNT signaling, controls the progenitor state and the switch towards the mesodermal fate. Sox2 acts antagonistically and promotes neural development. Tbx6 reinforces the mesodermal fate choice, represses the progenitor state and confers paraxial fate commitment. Our findings refine previous models and establish new concepts of the molecular principles of mammalian trunk development comprising NMP maintenance, lineage choice and mesoderm formation.
2017-08-17 | GSE93524 | GEO
Project description:Brachyury (Xbra/Xbra3) knock-down embryos of the frog Xenopus tropicalis were profiled to quantify neuro-mesodermal cell fate switches at a transcriptional level.
2013-09-19 | GSE48663 | GEO
Project description:Brachyury (Xbra/Xbra3) knock-down embryos of the frog Xenopus tropicalis were profiled to quantify neuro-mesodermal cell fate switches at a transcriptional level. Transcriptional profiling of Xbra/Xbra3 double morphants at early tadpole stage (RNA-Seq) in biological triplicates.
2013-09-19 | E-GEOD-48663 | biostudies-arrayexpress
Project description:The node and notochord are important signaling centers organizing dorso-ventral patterning of cells arising from neuro-mesodermal progenitors forming the embryonic body anlage. Due to the scarcity of notochordal progenitors and notochord cells, a comprehensive identification of regulatory elements driving notochord-specific gene expression has been lacking. Here we have used ATAC-seq analysis of FACS-purified notochordal cells from TS12-13 mouse embryos to identify 8921 putative enhancers of notochordal cells. In addition, we established a new model for generating notochordal cells in culture, and identified 3728 enhancers occupied by the essential notochordal regulators Brachyury (T) and/or Foxa2. We describe the regulatory landscape of the T locus comprising 8 putative enhancers occupied by these factors and confirmed the regulatory activity of 3 of these elements. Moreover, we characterized one new notochord enhancer, termed TNE2, in embryos. TNE2 complements the loss of TNE in the trunk notochord, and is essential for notochordal cell proliferation and differentiation in the tail. Our data demonstrate the essential role of Foxa2 in the choice of T expressing cells between the notochordal fate and the NMP/mesodermal trajectory
2023-10-31 | GSE235030 | GEO
Project description:We defined genome-wide regulatory inputs of the T-box transcription factors Brachyury (Xbra), Eomesodermin (Eomes) and VegT that maintain neuro-mesodermal stem cells and determine their bipotential fates in the Xenopus tropicalis frog embryo.
2013-09-19 | GSE48560 | GEO
Project description:We defined genome-wide regulatory inputs of the T-box transcription factors Brachyury (Xbra), Eomesodermin (Eomes) and VegT that maintain neuro-mesodermal stem cells and determine their bipotential fates in the Xenopus tropicalis frog embryo. Binding profiles for Xbra, Eomes and VegT in X. tropicalis embryos (ChIP-Seq)
2013-09-19 | E-GEOD-48560 | biostudies-arrayexpress
Project description:In the past decades, the paradigm of three germ layers formed by gastrulation has been modified by data suggesting an existence of neuromesodermal progenitors (NMPs) that arise during gastrulation and contribute to both spinal cord and adjacent paraxial mesoderm1-5. However, there lacks direct genetic lineage tracing evidence and functional assessment of NMPs in vivo. Here, we develop a dual recombinases-mediated genetic system to specifically trace and genetically ablate Brachyury+Sox2+ NMPs. Genetic lineage tracing results and single-cell RNA sequencing analysis show that NMPs contain three distinct uni-potent and bi-potent progenitor populations for progressive differentiation into neural and mesodermal fates. Genetic ablation of NMPs by diphtheria toxin reveals a critical role of NMPs in tail formation. This study provides in vivo genetic evidence for heterogeneity of NMPs in their cell fate determination and their functional role in developing embryos.
2023-04-11 | GSE229103 | GEO
Project description:The heterochronic genes Lin28a/b and let-7 are well-established regulators of invertebrate development, however their functions in patterning the mammalian body plan remain unexplored. In this study, we discovered a novel function of Lin28/let-7 in controlling caudal vertebrae number during body axis formation. We found that FoxD1-driven overexpression of Lin28a or LIN28B led to a striking increase in caudal vertebrae number, whereas loss of Lin28a stunted tail formation. Accordingly, perturbation of the let-7 microRNA family led to the opposite phenotypes. We further show that overexpressing Lin28a in embryos resulted in increased tail bud cell proliferation, whereas Lin28a KO decreased cellular proliferation. This was accompanied by a transcriptional shift, including down-regulation of the neural marker Sox2, and resulted in a pro-mesodermal phenotype with decreased proportions of neural tissue relative to mesoderm in Lin28a-overexpressing embryos. Strikingly, Lin28a KO and let-7 over-expression demonstrated opposite effects, suggesting that the Lin28/let-7 pathway acts upstream of the signaling pathways controlling the self-renewal and cell fate commitment of neuro-mesodermal progenitors. We propose that Lin28a/b activity controls the pool of caudal progenitors during tail development, promotes their self-renewal potential, is involved in controlling the balance of neural versus mesodermal cell fate decisions, and that progressive down-regulation of Lin28a allows for species-specific vertebral formula to be achieved. These findings suggest that Lin28/let-7 play a role in the regulation of tail length through heterochrony of the body plan.
2019-05-01 | GSE123193 | GEO
Project description:Stem cell fate decisions are tightly regulated by several processes, including epigenetic based histone modifications. Histone variants (HVs) represent a subfamily of epigenetic regulators implicated in early embryonic development, but their role in stem cell fate control has not been targeted. Here we reveal direct involvement of phosphorylation state of the histone variant H2A.X that allows control of self-renewal and differentiation of human pluripotent stem cells (hPSCs) and leukemic patient derived progenitors. Reduced levels of γH2A.X using either genetic approaches or chemical targeting allowed enhanced hPSC differentiation toward the mesodermal (hematopoietic) lineage with concomitant inhibition of ectodermal (neural) development. In contrast, activation and sustained levels of phosphorylated H2A.X enhanced hPSC ectodermal fate while suppressing mesodermal derived hematopoiesis. This controlled bifurcation of neural vs. hematopoietic differentiation correlated to occupancy of γH2A.X at gene loci associated with lineage selection. Drug modulation of H2A.X phosphorylation was extended to somatic cells to reveal the ability to induce differentiation of leukemic progenitors and serve as a biomarker in a cohort of adult leukemic patients. Our study uncovers a mechanism of cell-fate control of hPSCs extended to neoplastic progenitors through a histone variant epigenetic regulation
2021-03-09 | GSE164680 | GEO
Project description:β-Catenin is the major co-regulator of the Wnt signalling pathway. β-Catenin lysine 49 is post-translationally modified. The histone methyl transferase Ezh2 trimethylates β-catenin at lysine 49 and the acetyl transferase Cbp acetylates β-catenin at the same lysine. To determine the effects on gene expression embryonic stem cells containing either a Gfp tagged β-catenin wildtype (wt) or lysine 49 to alanine (K49A) loss of function mutation were analysed by micro array expression profiling. To determine the effects on gene expression in the pluripotent state two biological replicates of Gfp β-catenin wt and Gfp β-catenin K49A were analysed. The results showed that genes which affect pluripotency as well as differentiation were altered by β-catenin K49A mutation. To analyse the effects of gene expression during ES cell differentiation ES cells containing Gfp β-catenin wt or K49A were differentiated into mesodermal progenitors (mp) and neuronal progenitors (np). Two biological replicates were analysed by micro array expression profiling. Differentially expressed genes between Gfp β-catenin wt and K49A during differentiation were observed. Mesodermal marker genes like t-brachyury and cdx2 were not upregulated in mesodermal differentiation of Gfp β-catenin K49A Es cells.
2017-03-21 | E-MTAB-5523 | biostudies-arrayexpress