{"lab": {"title": "Siyuan Wang, YALE", "status": "current", "@type": ["Lab", "Item"], "uuid": "7f49b420-d2ae-4de4-820a-21403dc0749f", "display_title": "Siyuan Wang, YALE", "@id": "/labs/siyuan-wang-lab/", "correspondence": [{"contact_email": "c2l5dWFuLndhbmdAeWFsZS5lZHU=", "@id": "/users/774c29b8-db1e-48bc-9669-a3e380f435c2/", "display_title": "Siyuan Wang"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.7f49b420-d2ae-4de4-820a-21403dc0749f"]}}, "tags": ["many_replicates"], "award": {"uuid": "f959fce7-bd94-4a8d-961d-8c72a4eaa1ad", "project": "4DN", "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.", "status": "current", "@type": ["Award", "Item"], "center_title": "OFHHD - Schatz", "name": "1U01CA260701-01", "@id": "/awards/1U01CA260701-01/", "display_title": "GENOME ARCHITECTURE IN HUMAN GERMINAL CENTER B CELL DEVELOPMENT, MALIGNANCY, AND SOMATIC HYPERMUTATION", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "badges": [{"badge": {"display_title": "Inconsistent Replicate Info", "title": "Inconsistent Replicate Info", "@id": "/badges/inconsistent-replicate-info/", "description": "The experimental replicates belonging to this Experiment Set differ in some specific metadata fields", "warning": "Inconsistent Replicate Info", "badge_classification": "Warning", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "@type": ["Badge", "Item"], "status": "released", "uuid": "a4df9ff7-fe85-4672-86ac-7c38b5d9c853", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "messages": ["Inconsistent replicate information in microscope_configuration_master: Yale-Wang_lab_MINA_Nikon_Eclipse_Ti2-U_Jellyfish_Config1, Yale-Wang_lab_MINA_Nikon_Eclipse_Ti2-U_Jellyfish_Config2"]}], "status": "released", "aliases": ["siyuan-wang-lab:IMR90_control"], "accession": "4DNESDQV4VNJ", "condition": "IMR90 cells, untreated", "description": "Chromatin tracing (MINA) of an 840-kb region of chrX (chrX:77657854-78497854, GRCh38) in human female IMR-90 cells. The data presented here is pooled from 9 biological replicates.", "date_created": "2022-08-03T10:59:35.783404+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Chromatin tracing of chrX", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-06-26T17:05:43.508850+00:00"}, "public_release": "2022-08-08", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"uuid": "4849a206-c38c-482b-a268-58a71b89de1f", "@type": ["ExperimentMic", "Experiment", "Item"], "status": "released", "@id": "/experiments-mic/4DNEX72TVFZS/", "accession": "4DNEX72TVFZS", "display_title": "multiplexed FISH on IMR-90 - 4DNEX72TVFZS", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"uuid": "d58aedbe-1c6b-433e-b90c-775458049959", "@type": ["ExperimentMic", "Experiment", "Item"], "status": "released", "@id": "/experiments-mic/4DNEXM38AHPL/", "accession": "4DNEXM38AHPL", "display_title": "multiplexed FISH on IMR-90 - 4DNEXM38AHPL", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_headers": [{"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "status": "current", "@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"]}}, "body": "The experiments associated with this study are derived from either [d8f51a9c-1e1a-4a6c-9432-ddf7de64e836](https://data.4dnucleome.org/microscope-configurations/d8f51a9c-1e1a-4a6c-9432-ddf7de64e836) or [f0172a96-2bf5-4e6a-938d-f205c6e728c9](https://data.4dnucleome.org/microscope-configurations/f0172a96-2bf5-4e6a-938d-f205c6e728c9) microscopes.", "name": "microscope_note_cheng_et_al_", "award": {"@type": ["Award", "Item"], "@id": "/awards/2U01CA200059-06/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE II", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Microscope configuration - Cheng Y et al 2021", "status": "released", "aliases": ["4dn-dcic-lab:microscope_note_cheng_y_et_al_2021"], "options": {"filetype": "md", "collapsible": true, "default_open": true, "convert_ext_links": true}, "date_created": "2025-06-24T17:43:06.239219+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-06-24T17:51:49.392909+00:00"}, "schema_version": "2", "@id": "/static-sections/8e649b65-2a9f-4315-ae01-5cfcfc7e37be/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "8e649b65-2a9f-4315-ae01-5cfcfc7e37be", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.6f9809b1-b9b4-4f2f-8e6d-0762bce320ef"]}, "display_title": "Microscope configuration - Cheng Y et al 2021", "external_references": [], "content": "The experiments associated with this study are derived from either [d8f51a9c-1e1a-4a6c-9432-ddf7de64e836](https://data.4dnucleome.org/microscope-configurations/d8f51a9c-1e1a-4a6c-9432-ddf7de64e836) or [f0172a96-2bf5-4e6a-938d-f205c6e728c9](https://data.4dnucleome.org/microscope-configurations/f0172a96-2bf5-4e6a-938d-f205c6e728c9) microscopes.", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p>The experiments associated with this study are derived from either <a href=\"https://data.4dnucleome.org/microscope-configurations/d8f51a9c-1e1a-4a6c-9432-ddf7de64e836\" rel=\"noopener noreferrer\" target=\"_blank\">d8f51a9c-1e1a-4a6c-9432-ddf7de64e836</a> or <a href=\"https://data.4dnucleome.org/microscope-configurations/f0172a96-2bf5-4e6a-938d-f205c6e728c9\" rel=\"noopener noreferrer\" target=\"_blank\">f0172a96-2bf5-4e6a-938d-f205c6e728c9</a> microscopes.</p></div>"}, {"lab": {"uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "status": "current", "@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"]}}, "body": "Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).\n\nThis is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized around individual DNA bright Spots that are spatially linked together in a three-dimensional (3D) polymeric Trace.\nAdditional optional tables can complement this information and vary according to the specific dataset. \n\nThe full documentation is available here: https://fish-omics-format.readthedocs.io/", "name": "fof-ct.note", "award": {"@type": 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"role.owner", "userid.e4a22298-1da4-4e59-8a65-9e661f47fb48"]}, "display_title": "Note on FOF-CT file format", "external_references": [], "content": "Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).\n\nThis is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized around individual DNA bright Spots that are spatially linked together in a three-dimensional (3D) polymeric Trace.\nAdditional optional tables can complement this information and vary according to the specific dataset. \n\nThe full documentation is available here: https://fish-omics-format.readthedocs.io/", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p>Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).</p>\n<p>This is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized 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(2021)", "status": "current", "uuid": "9c1ed2e4-0c1d-48c1-85fb-a1b5d5a6db8b", "@type": ["Publication", "Item"], "url": "https://www.ncbi.nlm.nih.gov/pubmed/34749781", "ID": "PMID:34749781", "display_title": "Cheng Y et al. (2021) PMID:34749781", "abstract": "BACKGROUND: Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been  shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing lead to the  discovery of cohesin-independent TAD-like structures, also known as single-cell domains, which are highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains. RESULTS: Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components and transcription mostly do not affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains. CONCLUSIONS: In sum, this study suggests that single-cell domains are genome architecture building blocks independent of the tested major epigenetic components.", "title": "TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations.", "journal": "Genome biology", "@id": "/publications/9c1ed2e4-0c1d-48c1-85fb-a1b5d5a6db8b/", "date_published": "2021-11-08", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"status": "current", "display_title": "Cheng Y et al. (2021) PMID:34749781", "abstract": "BACKGROUND: Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been  shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing lead to the  discovery of cohesin-independent TAD-like structures, also known as single-cell domains, which are highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains. RESULTS: Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components and transcription mostly do not affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains. 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