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BRACHYURY orchestrates distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells

ABSTRACT: The transcription factor BRACHYURY (T, BRA) is one of the first markers of gastrulation and lineage specification in mammals. Despite its wide use and importance in stem cell and developmental biology, its genomic targets are largely unknown. Here, we used differentiated human embryonic stem cells to study the role of BRA in Bmp4-induced mesoderm and Activin-induced endoderm progenitors by ChIP-seq. We show that BRA has distinct genome-wide binding landscapes in these two populations. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE60606 | GEO | 2015/05/18

SECONDARY ACCESSION(S): PRJNA258643

REPOSITORIES: GEO

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BRACHYURY orchestrates distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells

Project description:The transcription factor BRACHYURY (T, BRA) is one of the first markers of gastrulation and lineage specification in mammals. Despite its wide use and importance in stem cell and developmental biology, its genomic targets are largely unknown. Here, we used differentiated human embryonic stem cells to study the role of BRA in Bmp4-induced mesoderm and Activin-induced endoderm progenitors by ChIP-seq. We show that BRA has distinct genome-wide binding landscapes in these two populations. 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. ChIP-seq of BRACHYURY (T, BRA) in two cell types: endoderm and mesoderm progenitors derived from human embryonic stem cells after 36 hours of growth in chemically-defined media (described in Bernardo et al., Cell Stem Cell, 2011, 9:144-155). Input DNA samples are included as a control.

2015-05-18 | E-GEOD-60606 | biostudies-arrayexpress

The molecular basis of specific functions of Brachyury and Eomes for mesoderm and endoderm lineage specification

Project description:The Tbx factors Eomesodermin (Eomes) and Brachyury instruct endoderm and mesoderm specification. Both Tbx factors have common large overlap in chromatin binding sites, however their embryonic phenotypes of mutants largely differ. In this study, we delineate the distinct binding patterns and gene target sets of Eomes and Brachyury providing a molecular model of distinct fate specification programs.

2023-07-26 | GSE194192 | GEO

Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells.

Project description: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.

| S-EPMC4483767 | biostudies-literature

Ectopic expression of the Brachyury transcription factor upregulates only a subset of notochord expressed genes

Project description:The key notochord transcription factor Brachyury was ectopically expressed in Ciona embryos under the control of the FoxAa cis-regulatory region (which drives expression in neural, endodermal and mesenchymal lineages in addition to notochord). Misexpression of Brachyury induced 925 genes compared to a control reporter plasmid (Bra>GFP). There was only modest overlap with a set of notochord-enriched genes previously identified by RNAseq of flow-sorted notochord cells, indicating that Brachyury is not a notochord master regulator gene as strictly defined.

2017-09-19 | GSE102142 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [IV]

Project description:The notochord is a defining feature of the chordates. The transcription factor Brachyury (Bra) is a key regulator of notochord fate but here we show that it is not a unitary master regulator in the model chordate Ciona. Ectopic Bra expression only partially reprograms other cell types to a notochord-like transcriptional profile and a subset of notochord-enriched genes are unaffected by CRISPR Bra disruption. We identify Foxa.a and Mnx as potential co-regulators and find that combinatorial cocktails are more effective at reprograming other cell types than Bra alone. We reassess the network relationships between Foxa.a, and other components of the notochord gene regulatory network and find that Foxa.a expression in the notochord is regulated by vegetal FGF signaling. It is a direct activator of Bra expression and has a binding motif that is significantly enriched in the regulatory regions of notochord-enriched genes. These and other results indicate that Bra and Foxa.a act together in a regulatory network dominated by positive feed-forward interactions, with neither being a classically-defined master regulator.er

2020-10-31 | GSE160547 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [III]

2020-10-31 | GSE160546 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [II]

2020-10-31 | GSE160545 | GEO

Brachyury controls Ciona notochord fate as part of a feedforward network [I]

2020-10-31 | GSE160544 | GEO

BRACHYURY knockdown in differentiating hESCs

Project description:Transcriptional profiling of H9 hESCs (wild type and BRACHYURY shRNA knockdown) differentiated for 36h or 72h in chemically-defined culture media supplemented with FGF2, LY294002 and either BMP4 or ActivinA.

2015-05-19 | E-MTAB-2912 | biostudies-arrayexpress

Targets of the transcription factor Brachyury in differentiating mouse ES cells

Project description:Brachyury (or T) is expressed in the primitive streak, tailbud and notochord of the early mouse embryo (Herrmann et al., 1990; Wilkinson et al., 1990). It plays a key role in early development: mouse embryos lacking functional Brachyury protein fail to gastrulate properly, do not form a differentiated notochord, and lack structures posterior to somite seven (Chesley, 1935; Dobrovolskaïa-Zavadskaïa, 1927; Naiche et al., 2005; Wilson et al., 1995; Wilson et al., 1993; Yanagisawa et al., 1981) We apply a ChIP-on-chip approach to identify targets of Brachyury during mouse ES cell differentiation. ES cells provide an abundant source of differentiating cells and the identification of Brachyury targets in such cells will shed light on the mechanisms of ES cell differentiation and, by analyzing the targets in the developing embryo, will reveal to what extent they provide a bone fide model of early mouse development.

2012-05-29 | GSE16646 | GEO

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