EXPERIMENT_TITLE: GSM3602089: Hi-C library corrected 1 rep 2; Homo sapiens; Hi-C
EXPERIMENT_DESIGN_LIBRARY_DESCRIPTOR_LIBRARY_CONSTRUCTION_PROTOC: Cells were lysed using 10 mM Tris-HCl, pH 8.0, 10 mM NaCl, 0.2% Igepal CA-630, 1x Protease Inhibitor in ddH2O Library prep was carried out using the in situ DNase Hi-C protocols (V. Ramani et al. Nat Protoc. 2016). Samples were barcoded during final library PCR and samples were demultiplexed prior to downstream analysis. Each library was sequenced two independent times, and the results were merged during downstream analysis.
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Pathogenic mutations in A-type nuclear lamins may dysregulate gene expression due to changes in chromatin organization into active (A) and inactive (B) compartments. To test this, we performed genome-wide chromosome conformation analyses (Hi-C) and transcriptome profiling (RNA-seq) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a haploinsufficient mutation for Lamin A/C that causes cardiac laminopathy. Mutant hiPSC-CM have marked electrophysiological, contractile, and gene expression alterations. While large-scale changes in chromatin topology are evident, differences in chromatin compartmentalization are limited to a few hotspots. These regions normally transition from A to B during cardiogenesis, but remain in A in mutant hiPSC-CM. Non-cardiac genes located within such aberrant domains are ectopically expressed, including the neuronal P/Q-type calcium channel CACNA1A. Pharmacological inhibition of the resulting currents partially mitigates elongation of field potential duration in mutant hiPSC-CM. On the other hand, A/B compartment changes do not explain most gene expression alterations observed in mutant hiPSC-CM, putting in perspective the role of chromatin organization dysregulation in cardiac laminopathy. Overall design: Hi-C analyses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) with a heterozygous R225X mutation (mutant), and hiPSC-CM from two isogenic control lines where such mutation was reverted to the wild-type allele using CRISPR/Cas9 (corrected); two biological replicates from independent differentiations per cell line.
SAMPLE_TITLE: Hi-C library corrected 1 rep 2
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "source_name", "VALUE": "Hi-C library corrected 1"}, {"TAG": "cell type", "VALUE": "human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)"}, {"TAG": "cell line", "VALUE": "R225R LMNA corrected 1 hiPSCs"}, {"TAG": "time point", "VALUE": "Day 14 of cardiac differentiation"}]
Pool_Member_@attributes_sample_title: Hi-C library corrected 1 rep 2
RUN_SET_RUN: [{"IDENTIFIERS": {"PRIMARY_ID": "SRR8568009", "SUBMITTER_ID": "GSM3602089_r1"}, "EXPERIMENT_REF": null, "Pool": {"Member": {"IDENTIFIERS": {"PRIMARY_ID": "SRS4359659", "EXTERNAL_ID": ["SAMN10921584", "GSM3602089"]}, "@attributes": {"member_name": "", "accession": "SRS4359659", "sample_name": "GSM3602089", "sample_title": "Hi-C library corrected 1 rep 2", "spots": "73961343", "bases": "11094201450", "tax_id": "9606", "organism": "Homo sapiens"}}}, "SRAFiles": {"SRAFile": [{"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR8568009", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR8568009/SRR8568009", "size": "4230163390", "date": "2019-02-12 14:55:28", "md5": "048d403567e7c404accb1c7f545fd15b", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR8568009.sralite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos5/sra-pub-zq-14/SRR008/568/SRR8568009.sralite.1", "size": "2777083190", "date": "2020-06-23 10:39:11", "md5": "9d471f31cbed89593ba850ce1a840e54", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_corrected.1_rep2_run1_R2.fastq.gz", "size": "3227752624", "date": "2020-02-05 03:22:49", "md5": "c06174bbfb34082f520a654acba1da14", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_corrected.1_rep2_run1_R1.fastq.gz", "size": "3133632785", "date": "2020-02-05 02:07:07", "md5": "602df2b427fb503fad7d6ec00ac5ff40", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]}, "CloudFiles": {"CloudFile": [null, null, null, null]}, "Statistics": {"Read": [null, null], "@attributes": {"nreads": "2", "nspots": "73961343"}}, "Databases": {"Database": {"Table": {"Statistics": {"Rows": null, "Elements": null, "@attributes": {"source": "meta"}}, "@attributes": {"name": "SEQUENCE"}}}}, "Bases": {"Base": [null, null, null, null, null], "@attributes": {"cs_native": "false", "count": "11094201450"}}, "@attributes": {"alias": "GSM3602089_r1", "accession": "SRR8568009", "total_spots": "73961343", "total_bases": "11094201450", "size": "4230162162", "load_done": "true", "published": "2019-02-13 18:25:19", "is_public": "true", "cluster_name": "public", "has_taxanalysis": "1", "static_data_available": "1"}}, {"IDENTIFIERS": {"PRIMARY_ID": "SRR8568010", "SUBMITTER_ID": "GSM3602089_r2"}, "EXPERIMENT_REF": null, "Pool": {"Member": {"IDENTIFIERS": {"PRIMARY_ID": "SRS4359659", "EXTERNAL_ID": ["SAMN10921584", "GSM3602089"]}, "@attributes": {"member_name": "", "accession": "SRS4359659", "sample_name": "GSM3602089", "sample_title": "Hi-C library corrected 1 rep 2", "spots": "77116037", "bases": "11567405550", "tax_id": "9606", "organism": "Homo sapiens"}}}, "SRAFiles": {"SRAFile": [{"Alternatives": null, "@attributes": {"cluster": "public", "filename": "SRR8568010", "url": "https://sra-pub-run-odp.s3.amazonaws.com/sra/SRR8568010/SRR8568010", "size": "4657206796", "date": "2019-02-12 14:57:53", "md5": "ecaf535dbc55f9a862b70272f1f96747", "version": "1", "semantic_name": "SRA Normalized", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": [null, null, null], "@attributes": {"cluster": "public", "filename": "SRR8568010.sralite", "url": "https://sra-downloadb.be-md.ncbi.nlm.nih.gov/sos5/sra-pub-zq-16/SRR008/568/SRR8568010.sralite.1", "size": "2896329096", "date": "2020-06-19 21:11:23", "md5": "9769785ef1eee99a2f03eec2410cfb4a", "version": "1", "semantic_name": "SRA Lite", "supertype": "Primary ETL", "sratoolkit": "1"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_corrected.1_rep2_run2_R2.fastq.gz", "size": "3525364434", "date": "2020-02-05 04:08:25", "md5": "256db17735c0961134a14fc11778fe1f", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}, {"Alternatives": null, "@attributes": {"cluster": "public", "filename": "HiC_corrected.1_rep2_run2_R1.fastq.gz", "size": "3422531866", "date": "2020-02-05 06:03:24", "md5": "c64572fd21460754bf0b3d413f57e892", "version": "1", "semantic_name": "fastq", "supertype": "Original", "sratoolkit": "0"}}]}, "CloudFiles": {"CloudFile": [null, null, null, null]}, "Statistics": {"Read": [null, null], "@attributes": {"nreads": "2", "nspots": "77116037"}}, "Databases": {"Database": {"Table": {"Statistics": {"Rows": null, "Elements": null, "@attributes": {"source": "meta"}}, "@attributes": {"name": "SEQUENCE"}}}}, "Bases": {"Base": [null, null, null, null, null], "@attributes": {"cs_native": "false", "count": "11567405550"}}, "@attributes": {"alias": "GSM3602089_r2", "accession": "SRR8568010", "total_spots": "77116037", "total_bases": "11567405550", "size": "4657205567", "load_done": "true", "published": "2019-02-13 18:25:19", "is_public": "true", "cluster_name": "public", "has_taxanalysis": "1", "static_data_available": "1"}}]