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Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons

ABSTRACT: We profiled chromatin accessibility and gene expression changes along the differentiation of human pluripotent stem cells to dopaminergic neurons. We integrated the epigenomic and transcriptomic profiles to infer the activity of transcription factors (TFs) and DNA regulatory regions such as enhancers and long non-coding RNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153005 | GEO | 2021/06/05

REPOSITORIES: GEO

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Dynamic landscape of chromatin accessibility and transcriptomic changes during differentiation of human embryonic stem cells into dopaminergic neurons.

Project description: Not available

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Project description:Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks and protects dopaminergic neurons against apoptosis. RNA-seq data for differentially expressed genes in the SNpc of En1+/- mice, En2 infused mice and 6-OHDA/En2 injection experiments.

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Murine epiSC control vs murine epiSC differentiated into dopaminergic neurons [miRNA]

Project description:Small-RNA profiling of mouse embryonic, epiblast-derived, stem cells (epiSC). epiSC differentiated towards the dopaminergic phenotype were compared to control untreated epiSC. EpiSc were derived from a Pitx3-GFP mouse allowing visualization of dopaminergic (GFP+) differentiation efficiency.

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Engrailed homeoprotein protects mesencephalic dopaminergic neurons from oxidative stress

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