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SRX3602889: GSM2948963: CTCF-IPS-Mull_I_Y-207.11; Mus musculus; ChIP-Seq
1 ILLUMINA (Illumina HiSeq 2000) run: 37.5M spots, 1.9G bases, 511.3Mb downloads

Submitted by: NCBI (GEO)
Study: Retinal Cell Type Epigenetic Memory Predicts Reprogramming Efficiency and Retinogenesis in 3D Organoid Cultures [ChIP-seq_Mm]
show Abstracthide Abstract
Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3 and Myc. Many of these induced pluripotent stem cells (iPSCs) retain an epigenetic memory of their cellular origins and this in turn may bias their subsequent differentiation. Differentiated neurons are difficult to reprogram and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes. We have recently developed a new method for reprogramming retinal neurons and successfully reprogrammed rod photoreceptors from the murine retina. Here we extended our retinal reprogramming to cone photoreceptors, bipolar neurons, amacrine/horizontal cell interneurons and Müller glia at two different stages of development. We scored the efficiency of reprogramming across all 5 retinal cell types at each developmental stage and we measured retinal differentiation from each iPSC line using a quantitative standardized scoring system called STEM-RET. We discovered that the rod photoreceptors and bipolar neurons had the lowest reprogramming efficiency but iPSCs derived from rods and bipolar cells had the best retinal differentiation. Epigenetic memory was analyzed by characterizing DNA methylation and performing ChIP-seq for 8 histone marks, Brd4, PolII and CTCF. The epigenetic data were integrated with RNA-Seq data from each iPSC line. Retinal cell types with a greater epigenetic barrier to reprogramming (rods and bipolars) are more likely to retain epigenetic memory of their cellular origins. In addition, we identified biomarkers of iPSCs that are predictive of retinal differentiation. This work will have implications for selection of cell populations for cell based therapy and for using reprogramming of purified cell populations to advance our understanding of the role of the epigenome in normal differentiation. Overall design: Examination of 8 different histone modifications and 3 transcription factors, transcriptome, DNA methylation in 33 different iPSC cell lines along with mESC Eb5
Sample: CTCF-IPS-Mull_I_Y-207.11
SAMN08405659 • SRS2870810 • All experiments • All runs
Organism: Mus musculus
Library:
Instrument: Illumina HiSeq 2000
Strategy: ChIP-Seq
Source: GENOMIC
Selection: ChIP
Layout: SINGLE
Construction protocol: After removal of IRMEFs, iPS cells were collected after washing with PBS. Then cells were subjected to crosslinking in 1% formaldehyde (Thermo scientific, 28906) for 10 minutes at room temperature, followed by the addition of glycine at the final concentration of 0.125 M to quench the reaction. After centrifuge, cells were washed with cold PBS, counted and pelleted as 10 million cells for each nuclei preparation. The nuclei were isolated and prepared for shearing using TruChIP chromatin shearing kit (Covaris, 520127) according to manufacturer's protocol. After shearing, ChIP was performed using the iDeal ChIP-seq kit (Diagenode, C01010051). The antibodies used were: anti-H3K4me3 (Diagenode, C15410003-50), anti-H3K4me2 (Abcam, ab7766), anti-H3K4me1 (Abcam, ab8895), anti-H3K9/14ac (Diagenode, C15410200), anti-H3K27ac (Abcam, ab4729), anti-H3K36me3 (Active Motif, 61101), anti-H3K27me3 (Active Motif, 39155), and anti-CTCF (Active Motif, 61311). After de-crosslinking, DNA was extracted using MinElute PCR-purification kit (Qiagen, 28006) or Agencourt AMPure XP beads (Beckman Coulter, A63881) and subjected to library preparation using NEBNext ChIP-Seq Library Prep Master Mix Set for illumina (NEB, E6240L). The ChIP experiments and library preparation for antibodies including anti-RNA polymerase II (Abcam, ab5095), anti-Brd4 (Bethyl Laboratories, A301-985A) and anti-H3K9me3 (Active Motif, 39161), were performed by Active Motif.
Experiment attributes:
GEO Accession: GSM2948963
Links:
Runs: 1 run, 37.5M spots, 1.9G bases, 511.3Mb
Run# of Spots# of BasesSizePublished
SRR651490337,531,5971.9G511.3Mb2018-01-29

ID:
4995822

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