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SRX5431807: GSM3630251: H1_END_FOXA2_gRNA_H3K27ac_ChIPseq_rep2; Homo sapiens; ATAC-seq
1 ILLUMINA (NextSeq 500) run: 56.5M spots, 4.2G bases, 1.6Gb downloads

Submitted by: NCBI (GEO)
Study: Single-cell RNA sequencing-based CRISPRi screening resolves molecular drivers of early human endoderm development [set 2]
show Abstracthide Abstract
Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. Yet, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human pluripotent stem cells (hPSCs) to END offers a tractable system to study the molecular basis of normal and defective human-specific END development. Here, we interrogated dynamics in chromatin accessibility during differentiation of hPSCs to END, predicting DNA-binding proteins that may drive this cell fate transition. We then combined single-cell RNA-seq with parallel CRISPR-perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. Following a few candidates, we revealed distinct impairments in the differentiation trajectories for mediators of TGFß signaling and expose a role for the FOXA2 transcription factor in priming human END competence for human foregut and hepatic endoderm specification. Together, this single-cell functional genomics study provides high-resolution insight on human END development. Overall design: CRISPRi screen of endodermal differentiation with a single-cell RNA readout. This submission contains the chromatin data from the paper.
Sample: H1_END_FOXA2_gRNA_H3K27ac_ChIPseq_rep2
SAMN11022774 • SRS4411725 • All experiments • All runs
Organism: Homo sapiens
Library:
Instrument: NextSeq 500
Strategy: ATAC-seq
Source: GENOMIC
Selection: other
Layout: SINGLE
Construction protocol: ATAC-seq samples were processed according to Buenrostro et. al with slight modifications. Briefly, approximately 50,000 cells were pelleted at 750 x g for 15 minutes at 4oC. After the addition of lysis buffer (10 mM Tris-Cl pH 7.4, 10 mM NaCl, 3 mM MgCl2, and 0.1% IGEPAl CA-630), nuclei were pelleted at 750 x g for 15 minutes at 4oC and the supernatent was discarded. Transposase reaction was performed at 37oC for 30 minutes. The purified, tagmented DNA was amplified for 9-10 cycles and size selected using AMPure XP beads (Beckman Coulter, A63881) as follows: 0.55X volume of 2X concentrated AMPure beads was added to the amplified DNA and incubated for 5 minutes at room temperature. The supernatant, containing low-molecular weight DNA, was collected in a separate tube by removing the beads using a magnetic rack. 1X volume of AMPure beads was added to the supernatant and incubated for 5 min at room temperature. The beads were washed twice with 75% ethanol and then air dried. The final purified library was eluted in EB buffer and sequenced (paired-end, 75-75) on a NextSeq500 or Hi-Seq2000 platform. Total RNA was isolated using Trizol Reagent (Invitrogen, 15596-018) according to the manufacturer's instructions. For quantitative PCR analysis, 1 μg of total RNA was reverse-transcribed using SuperScript III First-Strand Synthesis System (Thermo, 18080051). Bulk RNA-sequencing library preparation of H1 hESC and differentiated hEND was performed following a published protocol {Zhang:2012kc}. Briefly, 4 μg of total RNA was depleted of ribosomal RNA using Ribo-Zero rRNA Removal Kit (Epicentre, MRZH116) and then converted to cDNA. Final sequencing libraries were generated using dUTP (Thermo, R0133) incorporation and uracil-N-glycosylase (NEB, M0280) treatment to generate strand-specific RNA-seq libraries. The final libraries were sequenced at paired-end on a Hi-Seq2000 platform.
Experiment attributes:
GEO Accession: GSM3630251
Links:
Runs: 1 run, 56.5M spots, 4.2G bases, 1.6Gb
Run# of Spots# of BasesSizePublished
SRR863312156,540,7274.2G1.6Gb2019-04-17

ID:
7340469

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