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Series GSE84324 Query DataSets for GSE84324
Status Public on Mar 14, 2018
Title Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers. Deletion of Jmjd3, a histone demethylase for H3K27me3, at the pancreatic progenitor stage impaired the efficiency of endocrine cell fate transition and thereafter islet formation. Curiously, single-cell RNA-seq revealed that the transcriptome and developmental pathway of Ngn3-high cells were not affected by the deletion of Jmjd3. Our study indicates sequential chromatin events and identifies a crucial role for Jmjd3 in regulating the efficiency of the transition from Ngn3-low to Ngn3-high cells.
 
Overall design The overall goal of this study was to understand the process of pancreatic endocrine cell specification and the chromatin regulations of endocrine cell fate transition. Specifically, we performed RNA-seq analyses on Ngn3-low and Ngn3-high cells from E13.5 Ngn3-GFP pancreata, and on nascent β-cells from E17.5 Ins1-RFP pancreata. To study the dynamic changes in the promoter and enhancer landscape during endocrine fate transitions, we performed ChIP-seq of promoter related histone modifications (H3K27me3 and H3K4me3) and enhancer related histone modifications (H3K4me1 and H3K27ac) in purified Ngn3-low, Ngn3-high and nascent β cells. To investigate the occupancy of NeuroD1 in endocrine progenitors, we performed NeuroD1 ChIP-seq of E14.5 whole pancreatic cells. To test the role of a histone demethylase, Jmjd3, in regulating endocrine lineage specification, we analyzed single-cell transcriptomes of Ngn3-low and Ngn3-high cells from Jmjd3-deleted pancreas.
 
Contributor(s) Yu X, Qiu W, Yang L, Li L, Zhang Y
Citation(s) 29559448
Submission date Jul 12, 2016
Last update date Mar 21, 2019
Contact name Cheng-Ran Xu
Organization name Peking University
Department College of Life Sciences
Street address No.5 Yiheyuan Road Haidian District
City Beijing
State/province Beijing
ZIP/Postal code 100871
Country China
 
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (258)
GSM2231444 E13.5 Ngn3-low #1
GSM2231445 E13.5 Ngn3-low #2
GSM2231446 E13.5 Ngn3-high #1
Relations
BioProject PRJNA328935
SRA SRP078420

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

Supplementary file Size Download File type/resource
GSE84324_Bulk_Cell_RNA-seq_Gene_Read_Count.txt.gz 582.5 Kb (ftp)(http) TXT
GSE84324_Bulk_Cell_RNA-seq_Pooled_Normalized_Gene_RPKM.txt.gz 430.6 Kb (ftp)(http) TXT
GSE84324_H3K27ac_Ins1-positive.bedgraph.gz 227.5 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K27ac_Ngn3-high.bedgraph.gz 191.9 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K27ac_Ngn3-low.bedgraph.gz 217.3 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K27me3_Ins1-positive.bedgraph.gz 256.7 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K27me3_Ngn3-high.bedgraph.gz 222.9 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K27me3_Ngn3-low.bedgraph.gz 203.9 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me1_Ins1-positive.bedgraph.gz 327.7 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me1_Ngn3-high.bedgraph.gz 328.7 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me1_Ngn3-low.bedgraph.gz 268.0 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me3_Ins1-positive.bedgraph.gz 39.4 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me3_Ngn3-high.bedgraph.gz 145.9 Mb (ftp)(http) BEDGRAPH
GSE84324_H3K4me3_Ngn3-low.bedgraph.gz 105.3 Mb (ftp)(http) BEDGRAPH
GSE84324_Input_E14.5.bedgraph.gz 144.1 Mb (ftp)(http) BEDGRAPH
GSE84324_Input_Ins1-positive.bedgraph.gz 287.5 Mb (ftp)(http) BEDGRAPH
GSE84324_Input_Ngn3-high.bedgraph.gz 345.7 Mb (ftp)(http) BEDGRAPH
GSE84324_Input_Ngn3-low.bedgraph.gz 302.0 Mb (ftp)(http) BEDGRAPH
GSE84324_NeuroD1_E14.5.bedgraph.gz 65.4 Mb (ftp)(http) BEDGRAPH
GSE84324_Single-cell_RNA-seq_Gene_RPKM.txt.gz 5.2 Mb (ftp)(http) TXT
GSE84324_Single-cell_RNA-seq_Gene_Read_Count.txt.gz 3.3 Mb (ftp)(http) TXT
Raw data are available in SRA
Processed data is available on Series record

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