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Series GSE155677 Query DataSets for GSE155677
Status Public on Jan 27, 2022
Title Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler
Organisms Escherichia coli; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Other
Summary How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, we combined single-cell RNA-seq and single-cell ATAC-seq with cell-type-specific measurements of enhancer activity, DNA methylation and three-dimensional genome architecture to systematically map the regulatory landscape of neural differentiation in the mouse neocortex in vivo. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex.
 
Overall design scRNA-seq and scATAC-seq of the somsatosensory area of the E14.5 mouse cortex. Additionally, massively parallel reporter assay (MPRA) and MethylHiC from isolated cell populations, namely neuronal stem cells (NSC), intermediate progenitors (IPC), projection neurons (PN), obtained from the somatosensory area of the E14.5 mouse cortex. Functional validation of Neurog2 using Hi-C, RNA-seq and NOME-seq in GFP and Neurog2 in vivo overexpression via in utero electroporation.
 
Contributor(s) Noack F, Vangelisti S, Raffl G, Carido M, Diwakar J, Chong F, Bonev B
Citation(s) 35132236
Submission date Aug 04, 2020
Last update date Feb 23, 2022
Contact name Boyan Bonev
E-mail(s) boyan.bonev@helmholtz-munich.de
Organization name Helmholtz Zentrum M├╝nchen
Lab Bonev Lab
Street address Ingolst├Ądter Landstr. 1
City Neuherberg
State/province Deutschland
ZIP/Postal code 85764
Country Germany
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL25368 Illumina NovaSeq 6000 (Escherichia coli)
Samples (36)
GSM4710393 scRNA-seq E14.5 somatosensory cortex rep1
GSM4710394 scRNA-seq E14.5 somatosensory cortex rep2
GSM4710395 scATAC-seq E14.5 somatosensory cortex rep1
Relations
BioProject PRJNA655209
SRA SRP275808

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Supplementary file Size Download File type/resource
GSE155677_RAW.tar 44.0 Gb (http)(custom) TAR (of BED, BEDGRAPH, BW, FA, MTX, PICKLE, TAR, TSV, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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