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Transcription factor binding dynamics during human ES cell differentiation.

ABSTRACT: Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome-wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage-specific behaviour of selected factors. In addition to the orchestrated remodelling of the chromatin landscape, we find that the binding of several transcription factors is strongly associated with specific loss of DNA methylation in one germ layer, and in many cases a reciprocal gain in the other layers. Taken together, our work shows context-dependent rewiring of transcription factor binding, downstream signalling effectors, and the epigenome during human embryonic stem cell differentiation.

SUBMITTER: Tsankov AM

PROVIDER: S-EPMC4499331 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Transcription factor binding dynamics during human ES cell differentiation.

Tsankov Alexander M AM Gu Hongcang H Akopian Veronika V Ziller Michael J MJ Donaghey Julie J Amit Ido I Gnirke Andreas A Meissner Alexander A

Nature 20150201 7539

Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome-wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage-specific behaviour of selected factors. In addition to t ...[more]

PMID: 25693565

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Transcription factor binding dynamics during human ES cell differentiation

2015-02-19 | GSE61475 | GEO

Transcription factor binding dynamics during human ES cell differentiation

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2015-02-19 | E-GEOD-61475 | biostudies-arrayexpress

Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation.

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Dynamic transcription programs during ES cell differentiation towards mesoderm in serum versus serum-freeBMP4 culture.

Project description:BACKGROUND: Expression profiling of embryonic stem (ES) cell differentiation in the presence of serum has been performed previously. It remains unclear if transcriptional activation is dependent on complex growth factor mixtures in serum or whether this process is intrinsic to ES cells once the stem cell program has been inactivated. The aims of this study were to determine the transcriptional programs associated with the stem cell state and to characterize mesoderm differentiation between serum and serum-free culture. RESULTS: ES cells were differentiated as embryoid bodies in 10% FBS or serum-free media containing BMP4 (2 ng/ml), and expression profiled using 47 K Illumina(R) Sentrix arrays. Statistical methods were employed to define gene sets characteristic of stem cell, epiblast and primitive streak programs. Although the initial differentiation profile was similar between the two culture conditions, cardiac gene expression was inhibited in serum whereas blood gene expression was enhanced. Also, expression of many members of the Kruppel-like factor (KLF) family of transcription factors changed dramatically during the first few days of differentiation. KLF2 and KLF4 co-localized with OCT4 in a sub-nuclear compartment of ES cells, dynamic changes in KLF-DNA binding activities occurred upon differentiation, and strong bio-informatic evidence for direct regulation of many stem cell genes by KLFs was found. CONCLUSION: Down regulation of stem cell genes and activation of epiblast/primitive streak genes is similar in serum and defined media, but subsequent mesoderm differentiation is strongly influenced by the composition of the media. In addition, KLF family members are likely to be important regulators of many stem cell genes.

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Global dynamics of stage-specific transcription factor binding during thymocyte development.

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Early specification of dopaminergic phenotype during ES cell differentiation.

Project description:BackgroundUnderstanding how lineage choices are made during embryonic stem (ES) cell differentiation is critical for harnessing strategies for controlled production of therapeutic somatic cell types for cell transplantation and pharmaceutical drug screens. The in vitro generation of dopaminergic neurons, the type of cells lost in Parkinson's disease patients' brains, requires the inductive molecules sonic hedgehog and FGF8, or an unknown stromal cell derived inducing activity (SDIA). However, the exact identity of the responding cells and the timing of inductive activity that specify a dopaminergic fate in neural stem/progenitors still remain elusive.ResultsUsing ES cells carrying a neuroepithelial cell specific vital reporter (Sox1-GFP) and FACS purification of Sox1-GFP neural progenitors, we have investigated the temporal aspect of SDIA mediated dopaminergic neuron specification during ES cell differentiation. Our results establish that SDIA induces a dopaminergic neuron fate in nascent neural stem or progenitor cells at, or prior to, Sox1 expression and does not appear to have further instructive role or neurotrophic activity during late neuronal differentiation of neural precursors. Furthermore, we show that dopaminergic neurons could be produced efficiently in a monolayer differentiation paradigm independent of SDIA activity or exogenous signalling molecules. In this case, the competence for dopaminergic neuron differentiation is also established at the level of Sox1 expression.ConclusionDopaminergic neurons are specified early during mouse ES cell differentiation. The subtype specification seems to be tightly linked with the acquisition of a pan neuroectoderm fate.

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Identification of Three Early Phases of Cell-Fate Determination during Osteogenic and Adipogenic Differentiation by Transcription Factor Dynamics.

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Dynamics of Transcription Factor Binding Site Evolution.

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Transcription factor binding predicts histone modifications in human cell lines.

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2024-01-10 | GSE238276 | GEO

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