ArticleDevelopment (Cambridge, England)2015
Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells.
Article in Development (Cambridge, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 168 citations in OpenAlex.
- Engineered human induced pluripotent stem cell models reveal altered podocytogenesis in congenital heart disease-associated SMAD2 mutations.Nature biomedical engineering · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
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- Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment.Nature communications · 2025Article
- The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification.EMBO reports · 2025Article
- MitoScribe single-cell molecular recorder logs graded signaling dynamics into mitochondrial DNA.bioRxiv : the preprint server for biology · 2025Article
- Extended culture of 2D gastruloids to model human mesoderm development.Nature methods · 2025Article
- ModelingJournal of the American Heart Association · 2025Article
- Developmental gene expression in skull-base chordomas and chondrosarcomas.Journal of neuro-oncology · 2025Article
- An in vivo CRISPR screen in chick embryos reveals a role for MLLT3 in specification of neural cells from the caudal epiblast.Development (Cambridge, England) · 2025Article
- Templated Pluripotent Stem Cell Differentiation via Substratum-Guided Artificial Signaling.ACS biomaterials science & engineering · 2024Article
- Individual variation in the emergence of anterior-to-posterior neural fates from human pluripotent stem cells.Stem cell reports · 2024Article
- β-catenin mediates endodermal commitment of human ES cells via distinct transactivation functions.Cell & bioscience · 2024Article
- Brachyury promotes extracellular matrix synthesis through transcriptional regulation of Smad3 in nucleus pulposus.American journal of physiology. Cell physiology · 2024Article
- Trisomy 12 compromises the mesendodermal differentiation propensity of human pluripotent stem cells.In vitro cellular & developmental biology. Animal · 2024Article
- Cis-regulatory interfaces reveal the molecular mechanisms underlying the notochord gene regulatory network of Ciona.Nature communications · 2024Article
- TBXT dose sensitivity and the decoupling of nascent mesoderm specification from EMT progression in 2D human gastruloids.Development (Cambridge, England) · 2024Article
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- Injury-induced cooperation of InhibinβA and JunB is essential for cell proliferation in Xenopus tadpole tail regeneration.Scientific reports · 2024Article
- Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor brachyury (T, BRA) is one of the first markers of gastrulation and lineage specification in vertebrates. Despite its wide use and importance in stem cell and developmental biology, its functional genomic targets in human cells are largely unknown. Here, we use differentiating human embryonic stem cells to study the role of BRA in activin A-induced endoderm and BMP4-induced mesoderm progenitors. We show that BRA has distinct genome-wide binding landscapes in these two cell populations, and that BRA interacts and collaborates with SMAD1 or SMAD2/3 signalling to regulate the expression of its target genes in a cell-specific manner. Importantly, by manipulating the levels of BRA in cells exposed to different signalling environments, we demonstrate that BRA is essential for mesoderm but not for endoderm formation. Together, our data illuminate the function of BRA in the context of human embryonic development and show that the regulatory role of BRA is context dependent. Our study reinforces the importance of analysing the functions of a transcription factor in different cellular and signalling environments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.