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TBX3 advances the developmental chromatin landscape towards the hepatic fate

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240141 | GEO | 2025/04/08

REPOSITORIES: GEO

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TBX3 advances the developmental chromatin landscape towards the hepatic fate [RNA-seq]

Project description:Hepatocytes differentiate from definitive endoderm in response to external signaling cues, however it is unclear how the hepatic lineage is specified and how transcription factors shape the chromatin to allow gene expression. By mapping histone modifications using a human stem cell model of hepatic differentiation, enhancers were found to exhibit dynamic, stage specific regulation, with many primed at the definitive endoderm stage. While hepatic enhancers gained active histone modifications, non-hepatic enhancers lost H3K4me1 after hepatic specification. TBX3, and to lesser extend HNF4A, bound to the hepatic enhancers and formed an interdependent transcription factor network. TBX3 bound both hepatic enhancers and promoters with low levels of H3K4me1 and a strong TBX3 motif. However, TBX3 binding was transient and upon eviction from TBX3-bound regions, H3K4me1 increased at enhancers, while H3K4me3 was established at promoters. This suggests that TBX3 plays a role in identifying hepatic enhancers and promoters during specification, which will then be activated to drive cell idenity.

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TBX3 advances the developmental chromatin landscape towards the hepatic fate [ChIP-seq]

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TBX3 advances the developmental chromatin landscape towards the hepatic fate [RNA-seq II]

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TBX3 advances the developmental chromatin landscape towards the hepatic fate

Project description:TBX3 advances the developmental chromatin landscape towards the hepatic fate

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TBX3 advances the developmental chromatin landscape towards the hepatic fate [ChIP-seq]

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TBX3 advances the developmental chromatin landscape towards the hepatic fate [RNA-seq]

Project description:TBX3 advances the developmental chromatin landscape towards the hepatic fate [RNA-seq]

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TBX3 Directs Cell-Fate Decision toward Mesendoderm.

Project description:Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

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