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

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

PROVIDER: PRJNA641151 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12070831_1.fastq.gz	Fastqsanger.gz
	SRR12070831_2.fastq.gz	Fastqsanger.gz
	SRR12070832_1.fastq.gz	Fastqsanger.gz
	SRR12070832_2.fastq.gz	Fastqsanger.gz
	SRR12070833_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

2021-06-05 | GSE153005 | GEO

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

Project description:Chromatin architecture influences transcription by modulating the physical access of regulatory factors to DNA, playing fundamental roles in cell identity. Studies on dopaminergic differentiation have identified coding genes, but the relationship with non-coding genes or chromatin accessibility remains elusive. Using RNA-Seq and ATAC-Seq we profiled differentially expressed transcripts and open chromatin regions during early dopaminergic neuron differentiation. Hierarchical clustering of differentially expressed genes, resulted in 6 groups with unique characteristics. Surprisingly, the abundance of long non-coding RNAs (lncRNAs) was high in the most downregulated transcripts, and depicted positive correlations with target mRNAs. We observed that open chromatin regions decrease upon differentiation. Enrichment analyses of accessibility depict an association between open chromatin regions and specific functional pathways and gene-sets. A bioinformatic search for motifs allowed us to identify transcription factors and structural nuclear proteins that potentially regulate dopaminergic differentiation. Interestingly, we also found changes in protein and mRNA abundance of the CCCTC-binding factor, CTCF, which participates in genome organization and gene expression. Furthermore, assays demonstrated co-localization of CTCF with Polycomb-repressed chromatin marked by H3K27me3 in pluripotent cells, progressively decreasing in neural precursor cells and differentiated neurons. Our work provides a unique resource of transcription factors and regulatory elements, potentially involved in the acquisition of human dopaminergic neuron cell identity.

| S-EPMC8379280 | biostudies-literature

Proteome dynamics in iPSC-derived human dopaminergic neurons – part 3: dynamic SILAC to study local synthesis and trafficking of proteins

Project description:Dopaminergic neurons participate in fundamental physiological processes and are the cell type primarily affected in Parkinson’s disease (PD). Their analysis is challenging due to the intricate nature of their function, their involvement in diverse neurological processes, their heterogeneity and localization in deep brain regions. Consequently, most of the research on the protein dynamics of dopaminergic neurons has been performed in animal cells ex vivo. Here we use iPSC-derived, human mid-brain specific dopaminergic neurons to study general features of their proteome biology. We use differential dynamic SILAC labeling in combination with microfluidic devices to analyze local protein synthesis and transport between axons and soma. We report 105 potentially novel axonal markers and detect translocation of 269 proteins between axons and the soma in the time frame of our analysis (120 hours). Importantly, we provide evidence for local synthesis of 154 proteins in the axon and their retrograde transport to the soma. Our study provides a workflow and resource for future applications of quantitative proteomics in iPSC-derived human neurons

2024-09-12 | PXD051016 | Pride

Deriving Dopaminergic Neurons for Clinical Use. A Practical Approach.

Project description:Identification of new small molecules that regulate the step-wise differentiation of hPSC into dopaminergic neurons population. Furthermore, the naturally occurring steroid, guggulsterone, was found to be the most effective inducer of neural stem cells into dopaminergic neurons. Total RNA extracted at different stages of neural differentiation from human pluripotent stem cells

2013-04-24 | E-GEOD-42265 | biostudies-arrayexpress

Proteome dynamics in iPSC-derived human dopaminergic neurons – part 2: protein turnover dynamics using SILAC

Project description:Dopaminergic neurons participate in fundamental physiological processes and are the cell type primarily affected in Parkinson’s disease (PD). Their analysis is challenging due to the intricate nature of their function, their involvement in diverse neurological processes, their heterogeneity and localization in deep brain regions. Consequently, most of the research on the protein dynamics of dopaminergic neurons has been performed in animal cells ex vivo. Here we use iPSC-derived, human mid-brain specific dopaminergic neurons to study general features of their proteome biology. We use dynamic SILAC to measure the half-life of more than 4,300 proteins. We report uniform turnover rates of conserved protein complexes and identify several outliers in the mitochondrial outer membrane and mitophagy pathway. Our study provides a workflow and resource for future applications of quantitative proteomics in iPSC-derived human neurons.

2024-09-12 | PXD051015 | Pride

Proteome dynamics in iPSC-derived human dopaminergic neurons – part 1: comprehensive coverage of the proteome using DIA

Project description:Dopaminergic neurons participate in fundamental physiological processes and are the cell type primarily affected in Parkinson’s disease (PD). Their analysis is challenging due to the intricate nature of their function, their involvement in diverse neurological processes, their heterogeneity and localization in deep brain regions. Consequently, most of the research on the protein dynamics of dopaminergic neurons has been performed in animal cells ex vivo. Here we use iPSC-derived, human mid-brain specific dopaminergic neurons to study general features of their proteome biology. We cover the proteome to a depth of 9,409 proteins and use dynamic SILAC to measure the half-life of more than 4,300 proteins. Our study provides a workflow and resource for future applications of quantitative proteomics in iPSC-derived human neurons.

2024-09-12 | PXD050991 | Pride

Engrailed homeoprotein protects mesencephalic dopaminergic neurons from oxidative stress

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.

2015-09-24 | E-GEOD-72321 | biostudies-arrayexpress

RNA-SEQ of Satb1-knockdown in dopaminergic neurons from the mouse mid-brain

Project description:RNA-SEQ profiling of mouse dopaminergic neurons from the mouse mid-brain, with AAV1 injections using a Satb1 shRNA-EGFP construct or a scrambed shRNA-EGFP construct Murine midbrain dopaminergic neurons with Satb1 shRNA treatment or scrambled control

2015-07-27 | E-GEOD-70133 | biostudies-arrayexpress

RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain

Project description:RNA-SEQ profiling of mouse whole midbrain and dopaminergic neurons from the mouse mid-brain Murine whole midbrain and murine midbrain dopaminergic neurons

2015-07-27 | E-GEOD-64526 | biostudies-arrayexpress

embryo dopaminergic neurons tiling array

Project description:modENCODE_submission_467 This submission comes from a modENCODE project of Robert Waterston. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: Our experiments are designed to detect all C. elegans transcripts by hybridizing RNA to commerically available genome tiling arrays. To maximize the chances of detecting rare transcripts with limited expression in specific cells, we are extracting RNA from selected embryonic cells isolated by FACS and from postembryonic cells by use of the mRNA tagging method. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Keywords: Transcript tiling array analysis EXPERIMENT TYPE: Transcript tiling array analysis. BIOLOGICAL SOURCE: Strain: BY200 (engineered, target gene dat-1 tagged by GFP); Tissue: dopaminergic neurons (embryonic); Developmental Stage: Mixed stage of embryos 20dC; Genotype: dat-1::GFP (pRN2003); Sex: Hermaphrodite; NUMBER OF REPLICATES: 3; EXPERIMENTAL FACTORS: Strain BY200 (engineered, target gene dat-1 tagged by GFP); temperature 20; Developmental Stage Mixed stage of embryos 20dC; Tissue dopaminergic neurons (embryonic)

2010-08-04 | E-GEOD-23257 | biostudies-arrayexpress

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