ChIP-seq analysis of Brachyury (T) in invitro derived NMPs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE293442 | GEO | 2025/11/12
REPOSITORIES: GEO
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Project description:In vertebrate embryos, anterior tissues are generated early, followed by the other axial structures that emerge sequentially from a posterior growth zone. The genetic network driving posterior axial elongation in mice, and its disturbance in mutants with posterior truncation are not yet fully understood. We show that the combined expression of Cdx2 and T Brachyury is essential to establish the core signature of posterior axial progenitors. Cdx2 and T Brachyury are required for extension of a similar trunk portion of the axis. Simultaneous loss of function of these two genes disrupts axial elongation to a much greater extent than each single mutation alone. We identify and validate common targets for Cdx2 and T Brachyury in vivo including Wnt and Fgf pathway components active in the axial progenitor niche. Our data demonstrate that integration of the Cdx/Hox and T Brachyury transcriptional networks controls differential axial growth during vertebrate trunk elongation.
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Project description:This dataset contains spatiotemporal transcriptome information on different axial progenitors throughout mouse axis elongation. Neuromesodermal Progenitors (NMPs), Lateral and Paraxial Mesoderm Progenitors (LPMPs), and Notochord Progenitors (NotoPs) show distinct expression profiles. Extensive similarity exist between NMPs and their immediate mesoderm-committed descendants at each stage investigated. Over time transcriptional changes occur in LPMPs and NMPs, with the major change occurring in NMPs between early somitogenesis and completion of trunk morphogenesis. In contrast, NotoPs contain a more stable transcriptome over time.
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Project description:ChIP-seq analysis of Brachyury (T) in invitro derived NMPs
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Project description:During mammalian embryogenesis, axial elongation of the neural tube is critical for establishing the anterior-posterior body axis, but is difficult to interrogate directly because it occurs post-implantation. Here we report an organoid model of neural tube extension using human pluripotent stem cell (hPSC) aggregates that recapitulates the morphologic and temporal gene expression patterns of neural tube development. Axially extending organoids consisted of longitudinally elongated epithelial compartments and contained TBXT(+)SOX2(+) neuromesodermal progenitors, PAX6(+) Nestin(+) neural progenitor populations, and MEOX1(+) paraxial mesoderm populations. Wnt agonism stimulated axial extensions in a dose-dependent manner and elongated organoids displayed regionalized rostral-caudal HOX gene expression, with hindbrain (HOXB1) expression distinct from brachial (HOXC6) and thoracic (HOXB9) expression. CRISPR interference-mediated silencing of BMP inhibitors induced elongation phenotypes that mimicked murine knockout models, and knock-down of the downstream Wnt target, TBXT, increased neuroepithelial compartmentalization and resulted in multiple extensions. These results indicate the potent morphogenic capacity of hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.
2021-05-28 | GSE155382 | GEO
Project description:During mammalian embryogenesis, axial elongation of the neural tube is critical for establishing the anterior-posterior body axis, but is difficult to interrogate directly because it occurs post-implantation. Here we report an organoid model of neural tube extension using human pluripotent stem cell (hPSC) aggregates that recapitulates the morphologic and temporal gene expression patterns of neural tube development. Axially extending organoids consisted of longitudinally elongated epithelial compartments and contained TBXT(+)SOX2(+) neuromesodermal progenitors, PAX6(+) Nestin(+) neural progenitor populations, and MEOX1(+) paraxial mesoderm populations. Wnt agonism stimulated axial extensions in a dose-dependent manner and elongated organoids displayed regionalized rostral-caudal HOX gene expression, with hindbrain (HOXB1) expression distinct from brachial (HOXC6) and thoracic (HOXB9) expression. CRISPR interference-mediated silencing of BMP inhibitors induced elongation phenotypes that mimicked murine knockout models, and knock-down of the downstream Wnt target, TBXT, increased neuroepithelial compartmentalization and resulted in multiple extensions. These results indicate the potent morphogenic capacity of hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.
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Project description:We employed ATAC-seq to interrogate the chromatin accessibility landscape in neuromesodermal progenitor (NMP)-like cells derived from a human embryonic stem cell (hESC) line engineered to exhibit shRNA-mediated, tetracycline (Tet)-inducible knockdown of TBXT expression. TBXT shRNA hESCs were differentiated toward NMPs following a three day treatment in the presence of WNT and FGF agonists in the presence or absence of tetracycline and +/-Tet treated samples were harvested and analysed by ATAC-seq.
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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:To gain new mechanistic insights into highly-regulated lineage specification and morphogenetic processes during early embryogenesis, we applied ChIP-seq to identify transcriptional programs mediated by a key developmental regulator - Brachyury. Embryonic stem cells were differentiated into Brachyury-positive mesoendoderm cells. And, ChIP-seq experiments were carried out by two independent Brachyury antibodies.
2014-03-10 | E-GEOD-54978 | biostudies-arrayexpress
Project description:Chordoma is a rare malignant bone tumor on axial skeleton, locally invasive and has a high rate of recurrence. Despite extensive studies, the mechanisms of tumor recurrence after surgical intervention, as well as resistance to radiation and chemotherapy, remain elusive. In this study, cell lines PCH1 and PCH2 were established and characterized by chordoma specific markers. We found that the embryonic transcription factor brachyury inhibits taxol induced apoptosis in different cells, including PCH1 and U2OS cells. Brachyury regulated genes were identified in PCH1 and U2OS using microarray. Brachyury is an embryonic transcription factor involved in embryo development. We emplored the downstream genes related to apoptosis of Brachyury by microarray in different cell lines: U2OS, PCH1 and H460.
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