U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

SRX18337878: GSM6749200: cR_H9_EOS_d0_rep1, H3K27me3; Homo sapiens; ChIP-Seq
1 ILLUMINA (Illumina HiSeq 2500) run: 15.7M spots, 1.6G bases, 664.8Mb downloads

External Id: GSM6749200_r1
Submitted by: Bioinformatics, The Babraham Institute
Study: Epigenetic dynamics during capacitation of naïve human pluripotent stem cells [ChIP-seq]
show Abstracthide Abstract
Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine and the primary source for many novel cellular therapies. The development of naïve culture conditions has led to the expectation that these naïve hPSCs could overcome some of the limitations found in conventional (primed) hPSCs culture conditions, including recurrent epigenetic anomalies. Recent work has shown that transition to the primed state (or capacitation) is necessary for naïve hPSCs to acquire multi-lineage differentiation competence. This pluripotent state transition may recapitulate essential features of human peri-implantation development. Here we studied epigenetic changes during the transition between naïve and primed pluripotency, examining global genomic redistribution of histone modifications, chromatin accessibility, and DNA methylation, and correlating these with gene expression. We identify CpG islands, enhancers, and retrotransposons as hotspots of epigenetic dynamics between pluripotency states. Our results further reveal that hPSC resetting and subsequent capacitation rescue X chromosome-linked epigenetic erosion and reduce the ectoderm-biased gene expression of conventional primed hPSCs. Overall design: 2 lines of human naïve pluripotent stem cells (embryo-derived HNES1 and chemically reset cR-H9-EOS) were cultured in N2B27 and 2uM XAV939 for 10 days. After that the cells were split into two conditions: N2B27 + 2uM XAV939 + 3ng/ml Activin A + 10ng/ml FGF2 (XAF), or E8 medium, for extended maintenance. The experiment was performed with the cells on day 0 and 10, when the cells were cultured in XAV939; and one time point after transfer to maintenance conditions, at not less than 22 days of culture from the start of the experiment. Conventional hPSC cell line H9-EOS, which was a parental line for the chemically reset cR-H9-EOS was used as a control.
Sample: cR_H9_EOS_d0_rep1, H3K27me3
SAMN31825341 • SRS15826717 • All experiments • All runs
Organism: Homo sapiens
Library:
Name: GSM6749200
Instrument: Illumina HiSeq 2500
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: PAIRED
Construction protocol: 500.000 to 1.000.000 cells were used for ChIP per sample. Cross-linking was done with 1% formaldehyde in DMEM added directly to cells in culture dishes for 8 min at room temperature. Quenching was performed using 0.1M glycine (final concentration). The cells were washed with ice-cold PBS and scrapped with PBS with protease inhibitor cocktail (Cat. 11697498001, Roche). Lysis was performed in LB1 buffer (50mM HEPES-KOH pH7.5, 140mM NaCl, 1mM EDTA, 10% glycerol, 0.5% Igepal CA-630, 0.25% Triton X100, protease inhibitors) by rotating for 10 min at +4C, followed by centrifugation at 2000g for 5 min. The pellet was incubated in LB2 buffer (10mM Tris-HCl pH8.0, 200mM NaCl, 1mM EDTA, 0.5mM EGTA, protease inhibitors) by rotating for 5 min at +4C, followed by centrifugation at 2000g for 5 min. The pellet was resuspended in a buffer containing 50mM Tris-HCl pH8.0, 10mM EDTA, 1% SDS, the sonication was performed for 45 cycles, 30-sec intervals on/off. Debris was removed by centrifugation, and 10% from the sonicated material was saved as input. Prior to immunoprecipitation, 5ug antibody and 100ul Protein A beads were pre-incubated overnight at +4C in a total volume of 250ul, adjusted with PBS with 5mg/ml BSA, followed by three washes using the same solution. Immunoprecipitation was done by combining the sonicated material with the bead-antibody complexes, in a total volume of 400ul adjusted with ChIP dilution buffer (10mM Tris-HCl pH8.0, 100mM NaCl, 1mM EDTA, 0.5mM EGTA, 0.1% sodium deoxycholate, 0.5% N-lauroylsarcosine, 1% Triton X100, protease inhibitors), by rotating overnight at +4C. After the incubation, the beads were washed 6 times with RIPA buffer (50mM HEPES-KOH pH7.5, 500mM LiCl, 1mM EDTA, 1% Igepal CA-630, 0.7% sodium deoxycholate) followed by one wash in TE (10mM Tris-HCl pH8.0, 1mM EDTA). Reverse-crosslinking was done in elution buffer containing 1% SDS, 100mM sodium bicarbonate, and 200mM NaCl at 65C for 9-15 hours. The input sample was also reverse-crosslinked. After this step, the beads were removed from the mixture, and the remaining DNA in the solution was treated with 8 ug RNAse A for 1h at 37C, followed by 80ug proteinase K for 2 hours at 55C. DNA was purified using MinElute columns and then used for ChIP-Seq library preparation using the NEXTflex Rapid DNA-Seq Kit (NOVA-5144-02) according to the manufacturer's protocol with some minor modifications. Briefly, we amplified the final libraries with 4 cycles of PCR, then performed an AMPure XP-based size selection (0.5x to eliminate larger fragments followed by 1.8x to extract the smaller fragments), and then continued with 8 more PCR cycles on the size selected material. The final libraries were then cleaned up with 0.8x vol AMPure XP beads.
Runs: 1 run, 15.7M spots, 1.6G bases, 664.8Mb
Run# of Spots# of BasesSizePublished
SRR2236727815,657,6721.6G664.8Mb2023-10-03

ID:
25351443

Supplemental Content

Search details

See more...

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...