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Series GSE62193 Query DataSets for GSE62193
Status Public on Nov 02, 2014
Title Dissecting neural differentiation regulatory networks through epigenetic footprinting
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Human pluripotent stem cell derived models that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signaling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells (NPCs) in the embryonic and adult nervous system1-3. Use of a HES5 reporter enables the isolation distinct populations of human embryonic stem (ES) cell derived NPCs that represent building blocks of cortical development in vitro4. Here, we report the transcriptional and epigenomic analysis of six consecutive stages of human ES cell differentiation along the neural lineage aimed at modeling key cell fate decisions including specification, expansion and patterning during the ontogeny of neural stem and progenitor cells. In order to dissect the regulatory mechanisms that orchestrate the stage-specific differentiation process we developed a computational framework to infer key regulators of each cell state transition based on the progressive remodeling of the epigenetic landscape and then validated these through a pooled shRNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and show here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our reference maps and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation.
Overall design hESC were differentiated in vitro into 5 different NPC populations (NE, ERG, MRG, LRG and LNP) over a time period of 220 days. The hESCs and the first 3 NPC populations (NE, ERG, MRG) were subjected to ChIP-Seq for H3K4m3, H3K4me1, H3K27ac and H3K27me3 as well as RNA-Seq with two biological replicates each as well as whole genome bisulfite sequencing in singlicate. The last two populations (LRG, LNP) were both profiled by RRBS and the LRG populations also by RNA-Seq. In addition, each of the first three NPC populations were differentiated into more mature neuronal populations (NEdN, ERGdN, MRGdN). The LRG population was differentiated along the astrocyte fate (LRGdA). Each of these more mature populations was subjected to RNA-Seq in replicate. Finally, the NE and MRG populations were profiled for the transcription facctor OTX2 by ChIP-Seq.
Contributor(s) Meissner A, Elkabetz Y
Citation(s) 25533951
Submission date Oct 08, 2014
Last update date May 15, 2019
Contact name Michael Johannes Ziller
Organization name Max Planck Institute of Psychiatry
Department Translational Psychiatry
Lab Ziller lab
Street address Kraepelinstrasse 2-10
City Munich
ZIP/Postal code 80804
Country Germany
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (99)
GSM1521721 ESC_rep1_H3K27ac
GSM1521722 ESC_rep1_H3K27me3
GSM1521723 ESC_rep1_H3K4me1
BioProject PRJNA263414
SRA SRP048761

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE62193_AllSamples_geneExpression.fpkm_tracking.gz 3.8 Mb (ftp)(http) FPKM_TRACKING
GSE62193_ChIPseq_peaks.tar.gz 7.3 Mb (ftp)(http) TAR
GSE62193_cpgmethylation.bed.tar.gz 1001.1 Mb (ftp)(http) TAR
GSE62193_shRNAScreen_rawCounts.txt.gz 90.7 Kb (ftp)(http) TXT
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