2015
DOI: 10.1242/dev.117838
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Brachyury and SMAD signalling collaboratively orchestrate 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 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, … Show more

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Cited by 140 publications
(142 citation statements)
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References 74 publications
(161 reference statements)
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“…5D-G). In particular, induction of TBX6 , MSGN1 and MEOX1 was nearly abolished, in agreement with the established role of T in the expression of such genes (Chapman et al, 1996; Faial et al, 2015; Martin, 2015).
Fig.
…”
Section: Resultssupporting
confidence: 85%
See 1 more Smart Citation
“…5D-G). In particular, induction of TBX6 , MSGN1 and MEOX1 was nearly abolished, in agreement with the established role of T in the expression of such genes (Chapman et al, 1996; Faial et al, 2015; Martin, 2015).
Fig.
…”
Section: Resultssupporting
confidence: 85%
“…T mutants also present severe cardiovascular and placental defects (David et al, 2011; Inman and Downs, 2006; King et al, 1998). Furthermore, T was recently shown to specifically regulate mesoderm but not endoderm differentiation in hPSCs (Faial et al, 2015). …”
Section: Resultsmentioning
confidence: 99%
“…T also plays an essential role in the mesendoderm differentiation of the pluripotent stem cell in vitro (58,59). Determination of the mesendoderm lineage in early mouse embryo is always associated with the EMT process, during which epithelial epiblast cells lose apical-basal polarity and intercellular junctions (7,50).…”
Section: Discussionmentioning
confidence: 99%
“…BMP4 cooperates with FGF2 via the activation of ERK signaling to induce cardiac mesoderm formation by increasing expression of Brachyury protein, homeobox protein CDX-2, and homeobox protein NANOG 80 in a SMAD1-dependent manner, 81 while inhibiting endoderm differentiation. BMP4 signaling again plays a critical role in the terminal differentiation of cardiomyocyte progenitors into cardiomyocytes, but its effect at commitment stages is dependent on a precise balance with activin A, Nodal, and WNT signals in combinations that are specific not only to lineages, but specific also to progenitor clones.…”
Section: H1 Bmps and The Cardiovascular Systemmentioning
confidence: 99%