{"lab": {"uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "status": "current", "correspondence": [{"contact_email": "c2l5dWFuLndhbmdAeWFsZS5lZHU=", "@id": "/users/774c29b8-db1e-48bc-9669-a3e380f435c2/", "display_title": "Siyuan Wang"}], "display_title": "Siyuan Wang, YALE", "@type": ["Lab", "Item"], "title": "Siyuan Wang, YALE", "@id": "/labs/siyuan-wang-lab/", "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", "project": "4DN", "status": "current", "uuid": "f959fce7-bd94-4a8d-961d-8c72a4eaa1ad", "display_title": "GENOME ARCHITECTURE IN HUMAN GERMINAL CENTER B CELL DEVELOPMENT, MALIGNANCY, AND SOMATIC HYPERMUTATION", "@type": ["Award", "Item"], "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. 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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. 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"Experiment", "Item"], "uuid": "1e8513a7-a37d-49a0-87b1-d66cefa75f4b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "multiplexed FISH on A549 - 4DNEX32BZV4P", "external_references": [], "experiment_sets": [{"status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNES6SPZBS6", "uuid": "9e15530b-aaa8-447f-ab6a-a5d4e0054ab5", "@id": "/experiment-set-replicates/4DNES6SPZBS6/", "experimentset_type": "replicate", "display_title": "4DNES6SPZBS6", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "produced_in_pub": {"short_attribution": "Cheng Y et al. (2023)", "@id": "/publications/c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d/", "date_published": "2023-11-05", "uuid": "c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d", "authors": ["Cheng Y", "Hu M", "Yang B", "Jensen TB", "Yang T", "Yu R", "Ma Z", "Radda JSD", "Jin S", "Zang C", "Wang S"], "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.", "title": "Perturb-tracing enables high-content screening of multiscale 3D genome  regulators.", "ID": "PMID:36778402", "@type": ["Publication", "Item"], "status": "current", "display_title": "Cheng Y et al. (2023) PMID:36778402", "journal": "bioRxiv : the preprint server for biology", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"title": "Perturb-tracing enables high-content screening of multiscale 3D genome  regulators.", "date_published": "2023-11-05", "display_title": "Cheng Y et al. (2023) PMID:36778402", "short_attribution": "Cheng Y et al. (2023)", "authors": ["Cheng Y", "Hu M", "Yang B", "Jensen TB", "Yang T", "Yu R", "Ma Z", "Radda JSD", "Jin S", "Zang C", "Wang S"], "ID": "PMID:36778402", "@type": ["Publication", "Item"], "uuid": "c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d", "@id": "/publications/c4d07d85-7bc4-43d4-bc30-ee8b34c1ea8d/", "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.", "status": "current", "journal": "bioRxiv : the preprint server for biology", "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 A549", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSOO453IW/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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": []}