Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360989 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5168540_1.fastq.gz | Fastqsanger.gz | |||
| SRR5168540_2.fastq.gz | Fastqsanger.gz | |||
| SRR5168550_1.fastq.gz | Fastqsanger.gz | |||
| SRR5168550_2.fastq.gz | Fastqsanger.gz | |||
| SRR5168541_1.fastq.gz | Fastqsanger.gz |
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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.
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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.
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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
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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)
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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
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