{"lab": {"title": "Siyuan Wang, YALE", "@type": ["Lab", "Item"], "status": "current", "correspondence": [{"contact_email": "c2l5dWFuLndhbmdAeWFsZS5lZHU=", "@id": "/users/774c29b8-db1e-48bc-9669-a3e380f435c2/", "display_title": "Siyuan Wang"}], "display_title": "Siyuan Wang, YALE", "@id": "/labs/siyuan-wang-lab/", "uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.7f49b420-d2ae-4de4-820a-21403dc0749f"]}}, "award": {"center_title": "OFHHD - Schatz", "display_title": "GENOME ARCHITECTURE IN HUMAN GERMINAL CENTER B CELL DEVELOPMENT, MALIGNANCY, AND SOMATIC HYPERMUTATION", "description": "OFHHD: During the humoral immune response, somatic hypermutation (SHM) introduces point mutations in rearranged immunoglobulin (Ig) genes of activated germinal center (GC) B cells. SHM is essential for the fine-tuning of antibody affinity, the generation of B cells expressing high-affinity antibody, and the efficacy of many vaccines. Mistargeted SHM activities can lead to mutations and chromosomal translocations that contribute to the development of B cell lymphoma. Recent studies suggest that the three-dimensional (3D) organization of the genome regulates SHM targeting and mistargeting. However, it is largely unknown how the genome is spatially organized across multiple length scales in GC B cell development and lymphoma, and how 3D genome architecture mechanistically affects the targeting and mistargeting of SHM. Conventional approaches cannot address these questions in the primary GC tissue environment due to technical limitations. Here, we propose to apply a new method recently developed by our team, termed Multiplexed Imaging of Nucleome Architectures (MINA), to primary human tonsil tissue samples and malignant GC-derived human B cell lymphomas. We will investigate and test the association between SHM susceptibility and a variety of 3D nucleome architectures, including topologically associating domain (TAD) architecture, phase separation, and nuclear positioning of genomic regions relative to nuclear lamina, nucleoli, and nuclear pores. Through targeted genomic perturbations in human B cell lymphomas, we will test specific hypotheses linking SHM targeting elements to elevated chromatin looping interactions, TAD phase separation, nuclear pore proximity, and mutation vulnerability. Our study will significantly advance our understanding of the role of 3D genome architecture and nuclear organization in GC B cells undergoing SHM in both the developmental and tumorigenesis contexts. We expect this study to establish a new research paradigm and transform 3D nucleome investigations in immunobiology.", "uuid": "f959fce7-bd94-4a8d-961d-8c72a4eaa1ad", "status": "current", "name": "1U01CA260701-01", "@id": "/awards/1U01CA260701-01/", "project": "4DN", "@type": ["Award", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "aliases": ["siyuan-wang-lab:exp_neural-crest_shCHD7"], "protocol": {"status": "released", "display_title": "Biosample and Experimental protocol extracted from https://pubmed.ncbi.nlm.nih.gov/36778402/", "uuid": "7100b3de-ab17-4275-b4d7-beb2d874f277", "@type": ["Protocol", "Item"], "@id": "/protocols/7100b3de-ab17-4275-b4d7-beb2d874f277/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNEXZ1WOI1D", "biosample": {"biosource_summary": "H1-hESC differentiated to neural progenitor cell", "biosample_type": "in vitro differentiated cells", "display_title": "4DNBSG23W87M", "modifications_summary": "Viral Transduction disruption for CHD7 gene", "uuid": "5888c148-7d09-4043-99f1-2f41dd4ad319", "treatments_summary": "None", "status": "released", "@type": ["Biosample", "Item"], "accession": "4DNBSG23W87M", "@id": "/biosamples/4DNBSG23W87M/", "modifications": [{"genomic_change": "disruption", "status": "released", "display_title": "Viral Transduction disruption for CHD7 gene", "@type": ["Modification", "Item"], "uuid": "454a3f38-b570-4d05-bca1-1837d0acd5ce", "@id": "/modifications/454a3f38-b570-4d05-bca1-1837d0acd5ce/", "description": "Transfection of siRNA causing CHD7 Knockdown using shCHD7 to knockdown CHD7", "modification_type": "Viral Transduction", "target_of_mod": [{"feature_type": {"@type": ["OntologyTerm", "Item"], "uuid": "0231da78-1adc-4b8a-89b9-4f91908412a3", "@id": "/ontology-terms/SO:0000704/", "status": "released", "display_title": "gene", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "b9195c10-3256-4009-988c-19c413c41cf6", "display_title": "CHD7 gene", "status": "released", "@id": "/bio-features/b9195c10-3256-4009-988c-19c413c41cf6/", "organism_name": "human", "relevant_genes": [{"uuid": "ed1b54b3-73e9-4094-9e8d-72caacfc1ab9", "@id": "/genes/55636/", "@type": ["Gene", "Item"], "status": "released", "display_title": "CHD7", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@type": ["BioFeature", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "biosource": [{"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "display_title": "4DN DCIC, HMS", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "award": {"status": "current", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@id": "/awards/1U01CA200059-01/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "tissue": {"display_title": "stem cell", "uuid": "082f5be3-3617-4d3e-9ee9-78df53a71802", "term_id": "CL:0000034", "synonyms": ["animal stem cell"], "slim_terms": [{"status": "current", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "@id": "/ontology-terms/GO:0005623/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "released", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "@id": "/ontology-terms/CL:0000000/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/ontology-terms/CL:0000034/", "status": "released", "term_name": "stem cell", "@type": ["OntologyTerm", "Item"], "preferred_name": "stem cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "aliases": ["4dn-dcic-lab:h1wao1_untiered_from_encode"], "accession": "4DNSRVHDY783", "cell_line": {"@type": ["OntologyTerm", "Item"], "term_id": "EFO:0003042", "display_title": "H1-hESC", "term_name": "H1-hESC", "uuid": "c3f6e06f-900e-45f9-9c23-983c5673f58d", "synonyms": ["H1"], "@id": "/ontology-terms/EFO:0003042/", "slim_terms": [{"status": "current", "@id": "/ontology-terms/GO:0005623/", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "uuid": "72e16a19-eef3-46ca-a1b8-20e646e69675", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "released", "@id": "/ontology-terms/CL:0000000/", "@type": ["OntologyTerm", "Item"], "display_title": "cell", "uuid": "45d2b02e-130b-40db-8bf2-2288c6c57dcf", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "status": "released", "preferred_name": "H1-hESC", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "individual": {"@type": ["IndividualHuman", "Individual", "Item"], "protected_data": false, "uuid": "c97775b7-3d00-4132-9598-863797b8ef14", "@id": "/individuals-human/4DNIN3RG3ZKE/", "status": "released", "display_title": "4DNIN3RG3ZKE", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "description": "Untiered Homo sapiens male H1 embryonic stem cell (WA01)", "date_created": "2019-02-13T16:15:47.511051+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2019-09-19T19:54:39.038966+00:00"}, "biosource_type": "stem cell derived cell line", "cell_line_tier": "Unclassified", "public_release": "2019-02-13", "schema_version": "2", "project_release": "2019-02-13", "alternate_accessions": [], "@id": "/biosources/4DNSRVHDY783/", "@type": ["Biosource", "Item"], "uuid": "48561002-fe1b-4930-aa6d-fc57fcfcf163", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "H1-hESC - 4DNSRVHDY783", "external_references": [], "biosource_name": "H1-hESC", "biosource_category": ["H1-hESC", "Human stem cell"], "organism": {"display_title": "H. sapiens", "@type": ["Organism", "Item"], "status": "released", "name": "human", "uuid": "7745b647-ff15-4ff3-9ced-b897d4e2983c", "@id": "/organisms/9606/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "badges": [{"messages": ["Biosample missing culture_harvest_date", "Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing morphology_image", "Biosample is a stem cell line with unknown passage number missing karyotype"], "badge": {"title": "Biosample Metadata Incomplete", "display_title": "Biosample Metadata Incomplete", "status": "released", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group.", "badge_classification": "Warning", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@type": ["Badge", "Item"], "warning": "Biosample Metadata Incomplete", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "description": "Multiplexed FISH of chromosome 22 in neural crest cells from 2 coverslips where cells were differentiated from hESCs and transfected with CHD7 targeting shRNA causing CHD7 knock-down, Biological Replicate 1, Technical Replicate 1", "sop_mapping": {"has_sop": "No"}, "date_created": "2025-03-28T13:38:10.901643+00:00", "submitted_by": {"error": "no view permissions"}, "imaging_paths": [{"path": {"@id": "/imaging-paths/a40b97ca-ca0e-4d2a-aac0-00091ba396d2/", "display_title": "Chromosomes targeted by DAPI", "status": "released", "labeled_probe": "DAPI", "@type": ["ImagingPath", "Item"], "imaging_rounds": "0", "uuid": "a40b97ca-ca0e-4d2a-aac0-00091ba396d2", "target": [{"status": "released", "cellular_structure": "Chromosomes", "@id": "/bio-features/655728f9-d4ab-4dd2-971c-1627ab2c8d33/", "uuid": "655728f9-d4ab-4dd2-971c-1627ab2c8d33", "@type": ["BioFeature", "Item"], "display_title": "Chromosomes", "organism_name": "unspecified", "feature_type": {"term_id": "GO:0005575", "term_name": "cellular_component", "uuid": "e47e2bea-bc1e-4989-881c-521fc0b33529", "status": "released", "@type": ["OntologyTerm", "Item"], "display_title": "cellular_component", "preferred_name": "cellular_component", "@id": "/ontology-terms/GO:0005575/", "term_url": "http://purl.obolibrary.org/obo/GO_0005575", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "channel": "ch00"}, {"path": {"@id": "/imaging-paths/2240c1f0-739c-41c3-9308-6a1bc01fa599/", "display_title": "Yellow-green fiducial beads for drift correction on chromosome 22", "status": "released", "labeled_probe": "Fiducial bead", "@type": ["ImagingPath", "Item"], "override_display_title": "Yellow-green fiducial beads for drift correction on chromosome 22", "imaging_rounds": "1-14", "uuid": "2240c1f0-739c-41c3-9308-6a1bc01fa599", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "channel": "ch01"}, {"path": {"@id": "/imaging-paths/28d5a5ab-2a24-451e-a845-31d3b324305c/", "display_title": "G1 phase detection", "status": "released", "labeled_probe": "secondary antibody", "@type": ["ImagingPath", "Item"], "override_display_title": "G1 phase detection", "imaging_rounds": "0", "uuid": "28d5a5ab-2a24-451e-a845-31d3b324305c", "target": [{"preferred_label": "Geminin", "status": "released", "@id": "/bio-features/6da02096-25f1-4702-9328-e5be11886515/", "uuid": "6da02096-25f1-4702-9328-e5be11886515", "@type": ["BioFeature", "Item"], "display_title": "Geminin", "organism_name": "human", "relevant_genes": [{"status": "released", "@type": ["Gene", "Item"], "preferred_symbol": "GMNN", "geneid": "51053", "uuid": "a9ec607d-24e8-4cf9-bee2-3ce607581e4e", "display_title": "GMNN", "@id": "/genes/51053/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "feature_type": {"term_id": "SO:0000104", "term_name": "polypeptide", "uuid": "91f427e6-5246-4992-8123-b4f8fa9eef01", "status": "released", "@type": ["OntologyTerm", "Item"], "display_title": "protein", "preferred_name": "protein", "@id": "/ontology-terms/SO:0000104/", "term_url": "http://purl.obolibrary.org/obo/SO_0000104", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "channel": "ch02"}, {"path": {"@id": "/imaging-paths/4ca5c833-8543-45dc-a5fc-8eea4faf83f6/", "display_title": "27 TADs imaged on Chr22 imaged using ATTO 565 imaging probes", "status": "released", "labeled_probe": "imaging oligos", "@type": ["ImagingPath", "Item"], "override_display_title": "27 TADs imaged on Chr22 imaged using ATTO 565 imaging probes", "imaging_rounds": "1-14", "uuid": "4ca5c833-8543-45dc-a5fc-8eea4faf83f6", "target": [{"preferred_label": "27 TADs in Chr22", "status": "released", "@id": "/bio-features/d9645f1b-39e2-4a4f-81cb-cabf59432834/", "uuid": "d9645f1b-39e2-4a4f-81cb-cabf59432834", "@type": ["BioFeature", "Item"], "display_title": "27 TADs in Chr22", "organism_name": "human", "feature_type": {"term_id": "SO:0000001", "term_name": "region", "uuid": "41b7a2c5-f2d9-46b4-a49d-51502fe61bb3", "status": "released", "@type": ["OntologyTerm", "Item"], "display_title": "region", "preferred_name": "region", "@id": "/ontology-terms/SO:0000001/", "term_url": "http://purl.obolibrary.org/obo/SO_0000001", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "channel": "ch03"}, {"path": {"@id": "/imaging-paths/cea0b9b6-f018-4121-91cd-eeeefbb62e86/", "display_title": "27 TADs imaged on Chr22 imaged using Alexa Fluor 647 imaging probes", "status": "released", "labeled_probe": "imaging oligos", "@type": ["ImagingPath", "Item"], "override_display_title": "27 TADs imaged on Chr22 imaged using Alexa Fluor 647 imaging probes", "imaging_rounds": "1-14", "uuid": "cea0b9b6-f018-4121-91cd-eeeefbb62e86", "target": [{"preferred_label": "27 TADs in Chr22", "status": "released", "@id": "/bio-features/d9645f1b-39e2-4a4f-81cb-cabf59432834/", "uuid": "d9645f1b-39e2-4a4f-81cb-cabf59432834", "@type": ["BioFeature", "Item"], "display_title": "27 TADs in Chr22", "organism_name": "human", "feature_type": {"term_id": "SO:0000001", "term_name": "region", "uuid": "41b7a2c5-f2d9-46b4-a49d-51502fe61bb3", "status": "released", "@type": ["OntologyTerm", "Item"], "display_title": "region", "preferred_name": "region", "@id": "/ontology-terms/SO:0000001/", "term_url": "http://purl.obolibrary.org/obo/SO_0000001", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "channel": "ch04"}], "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-04-17T16:03:30.183885+00:00"}, "public_release": "2025-04-08", "schema_version": "3", "experiment_type": {"title": "multiplexed FISH", "status": "released", "assay_subclass_short": "FISH", "display_title": "multiplexed FISH", "experiment_category": "Microscopy", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "@type": ["ExperimentType", "Item"], "@id": "/experiment-types/multiplexed-fish/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "processed_files": [{"file_type_detailed": "FOF-CT - DNA-spot/trace core (csv)", "@id": "/files-processed/4DNFIRX951K7/", "file_size": 11814306, "display_title": "4DNFIRX951K7.csv", "accession": "4DNFIRX951K7", "file_format": {"uuid": "d13d06cf-218e-4f61-55f0-94f336118b2c", "display_title": "csv", "@type": ["FileFormat", "Item"], "@id": "/file-formats/csv/", "status": "released", "file_format": "csv", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "upload_key": "d5010cb8-1876-44c2-b5d8-3662a1992f58/4DNFIRX951K7.csv", "href": "/files-processed/4DNFIRX951K7/@@download/4DNFIRX951K7.csv", "file_type": "FOF-CT - DNA-spot/trace core", "@type": ["FileProcessed", "File", "Item"], "open_data_url": "https://4dn-open-data-public.s3.amazonaws.com/fourfront-webprod/wfoutput/d5010cb8-1876-44c2-b5d8-3662a1992f58/4DNFIRX951K7.csv", "file_classification": "processed file", "uuid": "d5010cb8-1876-44c2-b5d8-3662a1992f58", "external_references": [], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "track_and_facet_info": {"experimental_lab": "Siyuan Wang, YALE", "experiment_type": "multiplexed FISH", "experiment_bucket": "processed file", "assay_info": "27 TADs in Chr22, Chromosomes, Geminin", "dataset": "Multiplexed FISH in neural crest cells on Chr22", "condition": "shCHD7 targeted knocked-down", "replicate_info": "Biorep 1, Techrep 1", "biosource_name": "H1-hESC differentiated to neural progenitor cell", "lab_name": "Siyuan Wang, YALE"}}], "project_release": "2025-04-08", "reference_files": [{"uuid": "23ea2b0d-7ad8-4872-83fa-700e90c2adc0", "file_type": "target regions", "display_title": "4DNFITUM5ZTQ.bed.gz", "file_size": 278, "file_type_detailed": "target regions (bed)", "@id": "/files-reference/4DNFITUM5ZTQ/", "accession": "4DNFITUM5ZTQ", "file_classification": "ancillary file", "@type": ["FileReference", "File", "Item"], "status": "released", "static_content": [{"location": "tab:higlass", "description": "auto_generated_higlass_view_config", "content": {"display_title": "4DNFITUM5ZTQ", "uuid": "a105b479-2d7b-4a5b-8e6c-bec71b460ee8", "@id": "/higlass-view-configs/a105b479-2d7b-4a5b-8e6c-bec71b460ee8/", "@type": ["HiglassViewConfig", "UserContent", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.7677f8a8-79d2-4cff-ab0a-a967a2a68e39"]}}}], "file_format": {"display_title": "bed", "@id": "/file-formats/bed/", "file_format": "bed", "status": "released", "uuid": "69f6d609-f2ac-4c82-9472-1a13331b5ce9", "@type": ["FileFormat", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_relation": [{"experiment": {"@id": "/experiments-mic/4DNEXMZ481XR/", "uuid": "47021d2b-e1f3-4c5f-aa18-ebf75af678e5", "display_title": "multiplexed FISH on H1-hESC differentiated to neural progenitor cell - 4DNEXMZ481XR", "@type": ["ExperimentMic", "Experiment", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "relationship_type": "controlled by"}], "extinguishing_method": "DNase treatment", "microscope_settings_master": {"uuid": "af2eb527-a019-4443-9e74-c7ce17008e2f", "@id": "/microscope-settings-a2/af2eb527-a019-4443-9e74-c7ce17008e2f/", "display_title": "MicroscopeSettingA2 from 2021-03-15", "@type": ["MicroscopeSettingA2", "MicroscopeSetting", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "@id": "/experiments-mic/4DNEXZ1WOI1D/", "@type": ["ExperimentMic", "Experiment", "Item"], "uuid": "5f213c10-2538-469e-bbcf-5a53661d3ae3", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "multiplexed FISH on H1-hESC differentiated to neural progenitor cell - 4DNEXZ1WOI1D", "external_references": [], "experiment_sets": [{"accession": "4DNESHA7AS6L", "@id": "/experiment-set-replicates/4DNESHA7AS6L/", "experimentset_type": "replicate", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "status": "released", "uuid": "638ae607-229a-464e-a705-e1b593fa2863", "display_title": "4DNESHA7AS6L", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "produced_in_pub": {"display_title": "Cheng Y et al. (2023) PMID:36778402", "@id": "/publications/c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d/", "status": "current", "uuid": "c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d", "journal": "bioRxiv : the preprint server for biology", "abstract": "Three-dimensional (3D) genome organization becomes altered during development,  aging, and disease(1-23), but the factors regulating chromatin topology are  incompletely understood and currently no technology can efficiently screen for  new regulators of multiscale chromatin organization. Here, we developed an  image-based high-content screening platform (Perturb-tracing) that combines  pooled CRISPR screen, a new cellular barcode readout method (BARC-FISH), and  chromatin tracing. We performed a loss-of-function screen in human cells, and  visualized alterations to their genome organization from 13,000 imaging  target-perturbation combinations, alongside perturbation-paired barcode readout  in the same single cells. Using 1.4 million 3D positions along chromosome traces,  we discovered tens of new regulators of chromatin folding at different length  scales, ranging from chromatin domains and compartments to chromosome territory.  A subset of the regulators exhibited 3D genome effects associated with  loop-extrusion and A-B compartmentalization mechanisms, while others were largely  unrelated to these known 3D genome mechanisms. We found that the ATP-dependent  helicase CHD7, the loss of which causes the congenital neural crest syndrome  CHARGE(24) and a chromatin remodeler previously shown to promote local chromatin  openness(25-27), counter-intuitively compacts chromatin over long range in  different genomic contexts and cell backgrounds including neural crest cells, and  globally represses gene expression. The DNA compaction effect of CHD7 is  independent of its chromatin remodeling activity and does not require other  protein partners. Finally, we identified new regulators of nuclear architectures  and found a functional link between chromatin compaction and nuclear shape.  Altogether, our method enables scalable, high-content identification of chromatin  and nuclear topology regulators that will stimulate new insights into the 3D  genome functions, such as global gene and nuclear regulation, in health and  disease.", "short_attribution": "Cheng Y et al. (2023)", "ID": "PMID:36778402", "date_published": "2023-11-05", "authors": ["Cheng Y", "Hu M", "Yang B", "Jensen TB", "Yang T", "Yu R", "Ma Z", "Radda JSD", "Jin S", "Zang C", "Wang S"], "title": "Perturb-tracing enables high-content screening of multiscale 3D genome  regulators.", "@type": ["Publication", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"uuid": "c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d", "@id": "/publications/c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d/", "ID": "PMID:36778402", "display_title": "Cheng Y et al. (2023) PMID:36778402", "journal": "bioRxiv : the preprint server for biology", "@type": ["Publication", "Item"], "short_attribution": "Cheng Y et al. (2023)", "date_published": "2023-11-05", "title": "Perturb-tracing enables high-content screening of multiscale 3D genome  regulators.", "abstract": "Three-dimensional (3D) genome organization becomes altered during development,  aging, and disease(1-23), but the factors regulating chromatin topology are  incompletely understood and currently no technology can efficiently screen for  new regulators of multiscale chromatin organization. Here, we developed an  image-based high-content screening platform (Perturb-tracing) that combines  pooled CRISPR screen, a new cellular barcode readout method (BARC-FISH), and  chromatin tracing. We performed a loss-of-function screen in human cells, and  visualized alterations to their genome organization from 13,000 imaging  target-perturbation combinations, alongside perturbation-paired barcode readout  in the same single cells. Using 1.4 million 3D positions along chromosome traces,  we discovered tens of new regulators of chromatin folding at different length  scales, ranging from chromatin domains and compartments to chromosome territory.  A subset of the regulators exhibited 3D genome effects associated with  loop-extrusion and A-B compartmentalization mechanisms, while others were largely  unrelated to these known 3D genome mechanisms. We found that the ATP-dependent  helicase CHD7, the loss of which causes the congenital neural crest syndrome  CHARGE(24) and a chromatin remodeler previously shown to promote local chromatin  openness(25-27), counter-intuitively compacts chromatin over long range in  different genomic contexts and cell backgrounds including neural crest cells, and  globally represses gene expression. The DNA compaction effect of CHD7 is  independent of its chromatin remodeling activity and does not require other  protein partners. Finally, we identified new regulators of nuclear architectures  and found a functional link between chromatin compaction and nuclear shape.  Altogether, our method enables scalable, high-content identification of chromatin  and nuclear topology regulators that will stimulate new insights into the 3D  genome functions, such as global gene and nuclear regulation, in health and  disease.", "authors": ["Cheng Y", "Hu M", "Yang B", "Jensen TB", "Yang T", "Yu R", "Ma Z", "Radda JSD", "Jin S", "Zang C", "Wang S"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Target", "value": "27 TADs in Chr22, Chromosomes, Geminin", "combined": "Target: 27 TADs in Chr22, Chromosomes, Geminin"}, "experiment_summary": "multiplexed FISH on H1-hESC differentiated to neural progenitor cell", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSG23W87M/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing culture_harvest_date", "Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing morphology_image", "Biosample is a stem cell line with unknown passage number missing karyotype"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}