GSE68618

GSE GEO

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Aging-dependent demethylation of regulatory elements correlates with chromatin state and improved insulin secretion by pancreatic Î² cells

Organism: Mus musculus

Platform: GPL13112

Samples: 16

Experiment Types:

Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Methylation profiling by high throughput sequencing

Submitted: May 06 2015

Last Updated: May 15 2019

Status: Public on Sep 01 2015

Contact: Dana,,Avrahami Tzfati (Hadassah Hebrew University School of medicine)

Relations

BioProject: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA284579 SRA: https://www.ncbi.nlm.nih.gov/sra?term=SRP058569

Summary

Aging at the cellular level is driven by changes in gene activity and epigenetic state that are only partially understood. We performed a comprehensive epigenomic analysis of the pancreatic Î² cell, key player in glucose homeostasis and diabetes, in adolescent and very old mice. Globally, we observe a general methylation drift resulting in an overall more leveled methylome, suggesting that the maintenance of highly differential methylation patterns becomes compromised with advanced age. Importantly, we discover targeted changes in the methylation status of Î² cell proliferation and function genes that go against the global methylation drift, are specific to Î² cells, and correlate with repression of the proliferation program and activation of metabolic regulators. These targeted alterations frequently occur at distal cis-regulator elements, and are associated with specific chromatin marks and transcription factor occupancy in young Î² cells. Strikingly, we find the insulin secretory response to glucose much improved in mature Î² cells in mice, as predicted by the changes in methylome and transcriptome and in contrast to the decline in function observed in aged human Î² cells. Thus, aging of terminally differentiated cells in mammals is not always coupled to functional decline.

Overall Design

RNA-seq was done on 3 biological replicas from old and three from young beta cells. each sample originated from a pool of 5-10 mic.e H3K27me3 ChIP-seq was done with two replicas for old mice (pool of 4-7 mice) and the rest of the ChIPseq (H3K4me1, H3K27ac and young H3K27me3) was sone with one sample (pool of few mice). BIS-seq was done on one sample from a pool of 10 young mice and one sample of a pool of old mice (18-22 months old)

Analysis (11 steps)

View Data Processing

Processing steps for GSE68618

Illumina Casava-1.8.2 software was used for basecalling.
RNA-Seq: Low quality reads as well as ribosomal and other repeat sequences were filtered out before alignment.
RUM software was used for aligning reads to mouse genome mm9 and Refseq transcriptome and for transcript quantitation.
Differential expression analysis was carried out using a custom script implementing EdgeR software.
ChIP-Seq: Reads were aligned to mm9 genome using bowtie version 0.12.7 with parameters -v 3 -k 1 -m 1 --best --strata.
Redundant reads were discarded before creating bedgraph profiles.
Peak calling was done using HOMER for H3K4me1 and H3K27Ac marks at FDR=0.01 with respect to corresponding Input.
Peak calling using STAR was done for H3K27me3 marks at FDR=0.01.

Showing first 8 steps.

Supplementary Files (3)

GSE68618_RAW.tar Download

GSE68618_RawReadCounts.txt.gz Download

GSE68618_TrancriptFPKMCounts.txt.gz Download

GEO Samples (16)

GSM1677151 GSM1677152 GSM1677153 GSM1677154 GSM1677155 GSM1677156 GSM1677157 GSM1677158 GSM1677159 GSM1677160 GSM1677161 GSM1677162 GSM1677163 GSM1677164 GSM1677165 GSM1677166

Dataset Citations (1)

PubMed citation (PMID 26321660)

SRA Experiments (16) and Runs (38)

Total: 184071 MB

SRX1035135 SRP058569 RNA-Seq SINGLE

GSM1677151: OldBeta_Rep1_RNASeq; Mus musculus; RNA-Seq

Sample: SRS942558

BioProject: PRJNA284579

BioSample: SAMN03703607

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 15 months

strain: MIP-GFP/Bl6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (4)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034956	22141344	2214134400	1412.86	SRR2034956, SRR2034956.sralite, FGC0415_s_7_ATGTCA.fastq.gz	SRA
SRR2034957	22181520	2218152000	1417.4	SRR2034957, SRR2034957.sralite, FGC0415_s_8_ATGTCA.fastq.gz	SRA
SRR2034958	19525525	1952552500	1223.13	SRR2034958, SRR2034958.sralite, FGC0445_s_7_ATGTCA.fastq.gz	SRA
SRR2034959	19577331	1957733100	1199.95	SRR2034959, SRR2034959.sralite, FGC0445_s_8_ATGTCA.fastq.gz	SRA

SRX1035136 SRP058569 RNA-Seq SINGLE

GSM1677152: OldBeta_Rep2_RNASeq; Mus musculus; RNA-Seq

Sample: SRS942557

BioProject: PRJNA284579

BioSample: SAMN03703608

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16 months

strain: MIP-GFP/Bl6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (4)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034960	23047030	2304703000	1486.04	SRR2034960, SRR2034960.sralite, FGC0415_s_7_CCGTCC.fastq.gz	SRA
SRR2034961	23061548	2306154800	1489.27	FGC0415_s_8_CCGTCC.fastq.gz, SRR2034961, SRR2034961.sralite	SRA
SRR2034962	18908068	1890806800	1196.75	SRR2034962, SRR2034962.sralite, FGC0445_s_7_CCGTCC.fastq.gz	SRA
SRR2034963	18923131	1892313100	1173.26	SRR2034963, SRR2034963.sralite, FGC0445_s_8_CCGTCC.fastq.gz	SRA

SRX1035137 SRP058569 RNA-Seq SINGLE

GSM1677153: OldBeta_Rep3_RNASeq; Mus musculus; RNA-Seq

Sample: SRS942556

BioProject: PRJNA284579

BioSample: SAMN03703609

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 17 months

strain: MIP-GFP/Bl6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (4)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034964	15904217	1590421700	1025.78	FGC0415_s_7_GTCCGC.fastq.gz, SRR2034964, SRR2034964.sralite	SRA
SRR2034965	15916060	1591606000	1028.01	SRR2034965, SRR2034965.sralite, FGC0415_s_8_GTCCGC.fastq.gz	SRA
SRR2034966	20128736	2012873600	1272.7	FGC0445_s_7_GTCCGC.fastq.gz, SRR2034966, SRR2034966.sralite	SRA
SRR2034967	20164694	2016469400	1248.67	FGC0445_s_8_GTCCGC.fastq.gz, SRR2034967, SRR2034967.sralite	SRA

SRX1035138 SRP058569 RNA-Seq SINGLE

GSM1677154: YoungBeta_Rep1_RNASeq; Mus musculus; RNA-Seq

Sample: SRS942555

BioProject: PRJNA284579

BioSample: SAMN03703610

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: MIP-GFP/Bl6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (4)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034968	20083205	2008320500	1274.82	FGC0415_s_7_CTTGTA.fastq.gz, SRR2034968, SRR2034968.sralite	SRA
SRR2034969	20100434	2010043400	1277.8	SRR2034969, SRR2034969.sralite, FGC0415_s_8_CTTGTA.fastq.gz	SRA
SRR2034970	19527195	1952719500	1218.77	SRR2034970, SRR2034970.sralite, FGC0445_s_7_CTTGTA.fastq.gz	SRA
SRR2034971	19567945	1956794500	1195.26	FGC0445_s_8_CTTGTA.fastq.gz, SRR2034971, SRR2034971.sralite	SRA

SRX1035139 SRP058569 RNA-Seq SINGLE

GSM1677155: YoungBeta_Rep2_RNASeq; Mus musculus; RNA-Seq

Sample: SRS942554

BioProject: PRJNA284579

BioSample: SAMN03703611

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: MIP-GFP/Bl6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (4)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034972	20982899	2098289900	1340.64	SRR2034972, SRR2034972.sralite, FGC0415_s_7_AGTCAA.fastq.gz	SRA
SRR2034973	21023711	2102371100	1344.64	FGC0415_s_8_AGTCAA.fastq.gz, SRR2034973, SRR2034973.sralite	SRA
SRR2034974	18503219	1850321900	1160.75	SRR2034974, SRR2034974.sralite, FGC0445_s_7_AGTCAA.fastq.gz	SRA
SRR2034975	18546085	1854608500	1138.55	FGC0445_s_8_AGTCAA.fastq.gz, SRR2034975, SRR2034975.sralite	SRA

SRX1035140 SRP058569 ChIP-Seq SINGLE

GSM1677156: OldBeta_H3K4me1_ChIP; Mus musculus; ChIP-Seq

Sample: SRS942553

BioProject: PRJNA284579

BioSample: SAMN03703612

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16-18 months

strain: C57BL6

antibody: H3K4me1, ab8895, Abcam

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034976	33218109	1660905450	1034.12	FGC0277_s_2_GCCAAT.fastq.gz, SRR2034976, SRR2034976.sralite	SRA

SRX1035141 SRP058569 ChIP-Seq SINGLE

GSM1677157: OldBeta_H3K27me3_ChIP; Mus musculus; ChIP-Seq

Sample: SRS942552

BioProject: PRJNA284579

BioSample: SAMN03703613

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16-18 months

strain: C57BL6

antibody: H3K27me3, 07-449, upstate

Original files (1)

Pancreatic Beta Cells

Runs (2)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034977	57900812	2895040600	1574.77	FGC0605_s_7_GAGTGG.fastq.gz, SRR2034977, SRR2034977.sralite	SRA
SRR2034978	53456507	2672825350	1431.0	SRR2034978, SRR2034978.sralite, FGC0605_s_8_GAGTGG.fastq.gz	SRA

SRX1035142 SRP058569 ChIP-Seq SINGLE

GSM1677158: OldBeta_H3K4me1_Input; Mus musculus; ChIP-Seq

Sample: SRS942551

BioProject: PRJNA284579

BioSample: SAMN03703614

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16-18 months

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034979	43583834	2179191700	1347.4	FGC0277_s_2_TGACCA.fastq.gz, SRR2034979, SRR2034979.sralite	SRA

SRX1035143 SRP058569 ChIP-Seq SINGLE

GSM1677159: OldBeta_H3K27me3_Input; Mus musculus; ChIP-Seq

Sample: SRS942550

BioProject: PRJNA284579

BioSample: SAMN03703615

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16-18 months

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034980	65226664	3261333200	1785.34	SRR2034980.sralite, SRR2034980, FGC0857_s_1_CTTGTA.fastq.gz	SRA

SRX1035144 SRP058569 ChIP-Seq SINGLE

GSM1677160: YoungBeta_H3K4me1_ChIP; Mus musculus; ChIP-Seq

Sample: SRS942549

BioProject: PRJNA284579

BioSample: SAMN03703616

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: H3K4me1, ab8895, Abcam

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034981	36618515	1830925750	1137.74	SRR2034981, SRR2034981.sralite, FGC0277_s_2_ACAGTG.fastq.gz	SRA

SRX1035145 SRP058569 ChIP-Seq SINGLE

GSM1677161: YoungBeta_H3K27me3_ChIP; Mus musculus; ChIP-Seq

Sample: SRS942548

BioProject: PRJNA284579

BioSample: SAMN03703617

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: H3K27me3, 07-449, upstate

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034982	35282435	1764121750	1093.85	SRR2034982, SRR2034982.sralite, FGC0277_s_2_CAGATC.fastq.gz	SRA

SRX1035146 SRP058569 ChIP-Seq SINGLE

GSM1677162: YoungBeta_H3K27Ac_ChIP; Mus musculus; ChIP-Seq

Sample: SRS942547

BioProject: PRJNA284579

BioSample: SAMN03703618

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: H3K27Ac, 39685, Active Motif

Original files (1)

Pancreatic Beta Cells

Runs (2)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034983	21036907	1051845350	576.39	SRR2034983, SRR2034983.sralite, FGC0605_s_7_GCCAAT.fastq.gz	SRA
SRR2034984	19692056	984602800	530.61	FGC0605_s_8_GCCAAT.fastq.gz, SRR2034984, SRR2034984.sralite	SRA

SRX1035147 SRP058569 ChIP-Seq SINGLE

GSM1677163: Young_H3K4me1_or_H3K27me3_Input; Mus musculus; ChIP-Seq

Sample: SRS942546

BioProject: PRJNA284579

BioSample: SAMN03703619

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (1)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034985	44157721	2207886050	1364.75	SRR2034985.sralite, SRR2034985, FGC0277_s_2_CGATGT.fastq.gz	SRA

SRX1035148 SRP058569 ChIP-Seq SINGLE

GSM1677164: YoungBeta_H3K27Ac_Input; Mus musculus; ChIP-Seq

Sample: SRS942545

BioProject: PRJNA284579

BioSample: SAMN03703620

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (2)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034986	27340897	1367044850	852.06	FGC0466_s_7_GCCAAT.fastq.gz, SRR2034986, SRR2034986.sralite	SRA
SRR2034987	27871399	1393569950	875.35	SRR2034987, SRR2034987.sralite, FGC0466_s_8_GCCAAT.fastq.gz	SRA

SRX1035149 SRP058569 Bisulfite-Seq PAIRED

GSM1677165: OldBeta_BIS-Seq; Mus musculus; Bisulfite-Seq

Sample: SRS942543

BioProject: PRJNA284579

BioSample: SAMN03703621

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 16-18 months

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (3)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034988	97036309	19407261800	12134.95	FGC0225_s_3_1_fastq.gz, SRR2034988, SRR2034988.sralite, FGC0225_s_3_2…	SRA
SRR2034989	240688878	48137775600	30498.33	SRR2034989, SRR2034989.sralite, FGC0230_s_1_2_fastq.gz, FGC0230_s_1_1…	SRA
SRR2034990	219562678	43912535600	27090.02	FGC0261_s_2_1.fastq.gz, FGC0261_s_2_2.fastq.gz, SRR2034990, SRR203499…	SRA

SRX1035150 SRP058569 Bisulfite-Seq PAIRED

GSM1677166: YoungBeta_BIS-Seq; Mus musculus; Bisulfite-Seq

Sample: SRS942544

BioProject: PRJNA284579

BioSample: SAMN03703622

Platform: ILLUMINA

Instrument: Illumina HiSeq 2000

Organism: Mus musculus

Sample attributes

source_name: Pancreatic Beta Cells

age: 4-6 weeks

strain: C57BL6

antibody: N/A

Original files (1)

Pancreatic Beta Cells

Runs (3)

Run	Spots	Bases	Size (MB)	Files	Link
SRR2034991	197404164	39480832800	24767.67	FGC0220_s_1_1_fastq.gz, SRR2034991, SRR2034991.sralite, FGC0220_s_1_2…	SRA
SRR2034992	185532031	37106406200	24140.05	FGC0225_s_1_2_fastq.gz, SRR2034992, FGC0225_s_1_1_fastq.gz, SRR203499…	SRA
SRR2034993	213105508	42621101600	26711.49	SRR2034993.sralite, SRR2034993, FGC0260_s_2_2.fastq.gz, FGC0260_s_2_1…	SRA

Linked Publications (1)

Pseudotemporal Ordering of Single Cells Reveals Metabolic Control of Postnatal β Cell Proliferation.

Cell metabolism · 2017

Data Files (38)

Accession	File Name	Stored Type	Size	Download
—	FGC0220_s_1_1_fastq.gz	Bisulfite-Seq	24.2 GB	link
—	FGC0225_s_1_2_fastq.gz	Bisulfite-Seq	23.6 GB	link
—	FGC0225_s_3_1_fastq.gz	Bisulfite-Seq	11.9 GB	link
—	FGC0261_s_2_1.fastq.gz	Bisulfite-Seq	26.5 GB	link
—	SRR2034989	Bisulfite-Seq	29.8 GB	link
—	SRR2034993.sralite	Bisulfite-Seq	26.1 GB	link
—	FGC0277_s_2_GCCAAT.fastq.gz	ChIP-Seq	1.0 GB	link
—	FGC0277_s_2_TGACCA.fastq.gz	ChIP-Seq	1.3 GB	link
—	FGC0466_s_7_GCCAAT.fastq.gz	ChIP-Seq	852.1 MB	link
—	FGC0605_s_7_GAGTGG.fastq.gz	ChIP-Seq	1.5 GB	link
—	FGC0605_s_8_GCCAAT.fastq.gz	ChIP-Seq	530.6 MB	link
—	SRR2034978	ChIP-Seq	1.4 GB	link
—	SRR2034980.sralite	ChIP-Seq	1.7 GB	link
—	SRR2034981	ChIP-Seq	1.1 GB	link
—	SRR2034982	ChIP-Seq	1.1 GB	link
—	SRR2034983	ChIP-Seq	576.4 MB	link
—	SRR2034985.sralite	ChIP-Seq	1.3 GB	link
—	SRR2034987	ChIP-Seq	875.3 MB	link
—	FGC0415_s_7_CTTGTA.fastq.gz	RNA-Seq	1.2 GB	link
—	FGC0415_s_7_GTCCGC.fastq.gz	RNA-Seq	1.0 GB	link
—	FGC0415_s_8_AGTCAA.fastq.gz	RNA-Seq	1.3 GB	link
—	FGC0415_s_8_CCGTCC.fastq.gz	RNA-Seq	1.5 GB	link
—	FGC0445_s_7_GTCCGC.fastq.gz	RNA-Seq	1.2 GB	link
—	FGC0445_s_8_AGTCAA.fastq.gz	RNA-Seq	1.1 GB	link
—	FGC0445_s_8_CTTGTA.fastq.gz	RNA-Seq	1.2 GB	link
—	FGC0445_s_8_GTCCGC.fastq.gz	RNA-Seq	1.2 GB	link
—	SRR2034956	RNA-Seq	1.4 GB	link
—	SRR2034957	RNA-Seq	1.4 GB	link
—	SRR2034958	RNA-Seq	1.2 GB	link
—	SRR2034959	RNA-Seq	1.2 GB	link
—	SRR2034960	RNA-Seq	1.5 GB	link
—	SRR2034962	RNA-Seq	1.2 GB	link
—	SRR2034963	RNA-Seq	1.1 GB	link
—	SRR2034965	RNA-Seq	1.0 GB	link
—	SRR2034969	RNA-Seq	1.2 GB	link
—	SRR2034970	RNA-Seq	1.2 GB	link
—	SRR2034972	RNA-Seq	1.3 GB	link
—	SRR2034974	RNA-Seq	1.1 GB	link