{"ID": "PMID:35196517", "lab": {"title": "Yarui Diao, DUKE", "display_title": "Yarui Diao, DUKE", "@id": "/labs/yarui-diao-lab/", "@type": ["Lab", "Item"], "correspondence": [{"contact_email": "eWFydWkuZGlhb0BkdWtlLmVkdQ==", "@id": "/users/0a3d76d8-eebc-420f-b4f9-4012ad0d5976/", "display_title": "Yarui Diao"}], "status": "current", "uuid": "db4585e0-aacf-415b-b0e6-cb028e1c428f", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.db4585e0-aacf-415b-b0e6-cb028e1c428f"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/35196517", "award": {"display_title": "THE 4D NUCLEOME OF MUSCLE REGENERATION IN ISCHEMIA-INDUCED TISSUE DAMAGE AND REPAIR", "name": "1U01HL156064-01", "status": "current", "description": "NI-OFHHD: Ischemia, caused by restriction of blood flow, often results in severe tissue damage. Critical limb ischemia (CLI) is a serious condition in which peripheral artery disease (PAD) leads to irreversible limb muscle damage. About 40% of CLI patients undergo limb amputation one year after diagnosis, and 50% die after five years. Current treatment options focus on improving limb perfusion but these often fail to prevent disease progression, pointing to a critical need for a deeper understanding of the basic mechanisms regulating human muscle regeneration and how they are disrupted by ischemic damage. In the long-term, this information may lead to new regenerative treatment strategies for limb salvage that are independent of limb perfusion. Recent studies suggest that failure of skeletal muscle regeneration is key to determining tissue loss in CLI versus repair. Successful muscle regeneration requires the orchestrated activation, proliferation and differentiation of muscle stem cells (MuSCs, also known as satellite cells) that are normally quiescent. In our preliminary analysis of MuSCs from one representative CLI patient, we found that the transcription of genes important for MuSC regeneration are dysregulated in ischemia, and that these changes are associated with rearrangements in 3D chromatin organization. These finding support the hypothesis that CLI involves a failure in the normal dynamic reorganization of 3D chromatin structure that orchestrates the regeneration of MuSCs. The overall objectives of this study are to identify the spatial-temporal changes of chromatin organization (the 4D nucleome, 4DN) normally associated with regenerative human MuSCs, and to understand the functional consequences of defects in this mechanism for muscle damage in CLI.", "@id": "/awards/1U01HL156064-01/", "center_title": "Diao", "uuid": "9177c497-db1f-457b-903b-aa1464ee0fb2", "@type": ["Award", "Item"], "project": "4DN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "HiCAR is a robust and sensitive method to analyze open-chromatin-associated  genome organization.", "status": "current", "aliases": ["4dn-dcic-lab:diao_lab_hicar_method_PMID35196517"], "authors": ["Wei X", "Xiang Y", "Peters DT", "Marius C", "Sun T", "Shan R", "Ou J", "Lin X", "Yue F", "Li W", "Southerland KW", "Diao Y"], "journal": "Molecular cell", "abstract": "The long-range interactions of cis-regulatory elements (cREs) play a central role  in gene regulation. cREs can be characterized as accessible chromatin sequences.  However, it remains technically challenging to comprehensively identify their  spatial interactions. Here, we report a new method HiCAR (Hi-C on accessible  regulatory DNA), which utilizes Tn5 transposase and chromatin proximity ligation,  for the analysis of open-chromatin-anchored interactions with low-input cells. By  applying HiCAR in human embryonic stem cells and lymphoblastoid cells, we  demonstrate that HiCAR identifies high-resolution chromatin contacts with an  efficiency comparable with that of in situ Hi-C over all distance ranges.  Interestingly, we found that the \"poised\" gene promoters exhibit silencer-like  function to repress the expression of distal genes via promoter-promoter  interactions. Lastly, we applied HiCAR to 30,000 primary human muscle stem cells  and demonstrated that HiCAR is capable of analyzing chromatin accessibility and  looping using low-input primary cells and clinical samples.", "categories": ["technology development"], "date_created": "2023-05-19T14:19:23.419959+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-05-19T14:23:40.107401+00:00"}, "date_published": "2022-03-17", "public_release": "2023-05-19", "schema_version": "2", "project_release": "2023-05-19", "contributing_labs": [{"correspondence": [{"contact_email": "a2V2aW4uc291dGhlcmxhbmRAZ21haWwuY29t", "@id": "/users/526f4a59-6282-4790-bf5e-033112ab31d8/", "display_title": "Kevin Southerland"}], "display_title": "Kevin Southerland, DUKE", "status": "current", "uuid": "876b01d0-9048-44bd-83be-aa84a7a8c2ed", "@id": "/labs/kevin-southerland-lab/", "@type": ["Lab", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.876b01d0-9048-44bd-83be-aa84a7a8c2ed"]}}], "@id": "/publications/bf36ca33-861b-4036-b34a-144e022ef993/", "@type": ["Publication", "Item"], "uuid": "bf36ca33-861b-4036-b34a-144e022ef993", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Wei X et al. (2022) PMID:35196517", "external_references": [], "short_attribution": "Wei X et al. (2022)", "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}