{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:49:27Z","timestamp":1790858967213,"version":"4.1.0"},"reference-count":71,"publisher":"American Society for Clinical Investigation","issue":"10","funder":[{"DOI":"10.13039\/100009455","name":"West Virginia University","doi-asserted-by":"crossref","award":["P20GM121322"],"award-info":[{"award-number":["P20GM121322"]}],"id":[{"id":"10.13039\/100009455","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["R01 HL151390"],"award-info":[{"award-number":["R01 HL151390"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,21]]},"abstract":"<jats:p>\n                    NOD-like receptor 12 (NLRP12) is a member of the nucleotide-binding domain and leucine-rich repeat containing receptor inflammasome family that plays a central role in innate immunity. We previously showed that DNA damage upregulated\n                    <jats:italic>NLRP12<\/jats:italic>\n                    in hematopoietic stem cells (HSCs) of mice deficient in the DNA repair gene\n                    <jats:italic>Fanca<\/jats:italic>\n                    . However, the role of NLRP12 in HSC maintenance is not known. Here, we show that persistent DNA damage\u2013induced NLRP12 improves HSC function in both mouse and human models of DNA repair deficiency and aging. Specifically, treatment of\n                    <jats:italic>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice with the DNA cross-linker mitomycin C or ionizing radiation induces\n                    <jats:italic>NLRP12<\/jats:italic>\n                    upregulation in phenotypic HSCs.\n                    <jats:italic>NLRP12<\/jats:italic>\n                    expression is specifically induced by persistent DNA damage. Functionally, knockdown of\n                    <jats:italic>NLRP12<\/jats:italic>\n                    exacerbates the repopulation defect of\n                    <jats:italic>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    HSCs. Persistent DNA damage\u2013induced NLRP12 was also observed in the HSCs from aged mice, and depletion of NLRP12 in these aged HSCs compromised their self-renewal and hematopoietic recovery. Consistently, overexpression of NLRP12 substantially improved the long-term repopulating function of\n                    <jats:italic>\n                      Fanca\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    and aged HSCs. Finally, persistent DNA damage\u2013induced NLRP12 maintains the function of HSCs from patients with FA or aged donors. These results reveal a potentially novel role of NLRP12 in HSC maintenance and suggest that NLRP12 targeting has therapeutic potential in DNA repair disorders and aging.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.133365","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T11:01:32Z","timestamp":1589972492000},"source":"Crossref","is-referenced-by-count":11,"title":["Persistent DNA damage\u2013induced NLRP12 improves hematopoietic stem cell function"],"prefix":"10.1172","volume":"5","author":[{"given":"Qiqi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."},{"name":"Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."},{"name":"Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabliha Ahmed","family":"Chowdhury,1","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habibul Hasan","family":"Mazumder","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-537X","authenticated-orcid":true,"given":"Wei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia, USA."},{"name":"Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University Cancer Institute, Morgantown, West Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-746412"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160168"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2016.04.002"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nri3433"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature05862"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/stem.437"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600542"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.01.036"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm1578"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.055269"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200301000-00011"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2009.01.008"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1370505"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.002"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-427740"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.03.014"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-1156"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv227"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1186\/s40246-015-0054-y","article-title":"Update of the human and mouse Fanconi anemia genes","volume":"9","author":"Dong","year":"2015","journal-title":"Hum Genomics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103847"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI92069"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3088"},{"key":"B23"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.242"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003885"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.07.006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601048"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708616105"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.012"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.10.022"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00567-1"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-387332"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5668"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1590\/S1415-475738420150019"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.07.003"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703683114"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E16-01-0017"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.026"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr230"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C900032200"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq064"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.459"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2017.09.005"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nature14131"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69032"},{"key":"B46","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.13213.1","article-title":"Recent advances in understanding hematopoiesis in Fanconi Anemia","volume":"7","author":"Bagby","year":"2018","journal-title":"F1000Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.9.5286-5294.2003"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr057"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.03.018"},{"key":"B50","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11686","article-title":"Stepwise phosphorylation of p65 promotes NF-\u03baB activation and NK cell responses during target cell recognition","volume":"7","author":"Kwon","year":"2016","journal-title":"Nat Commun"},{"issue":"20","key":"B51","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20205200","article-title":"MicroRNA mediate visfatin and resistin induction of oxidative stress in human osteoarthritic synovial fibroblasts via NF-\u03baB pathway","volume":"20","author":"Cheleschi","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.1038\/srep18127","article-title":"Fancb deficiency impairs hematopoietic stem cell function","volume":"5","author":"Du","year":"2015","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-278226"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-05-349084"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.158"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-309179"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s40778-017-0087-3"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0087-z"},{"key":"B59","doi-asserted-by":"crossref","DOI":"10.1155\/2012\/165107","article-title":"Hematopoietic stem and progenitor cells as effectors in innate immunity","volume":"2012","author":"Granick","year":"2012","journal-title":"Bone Marrow Res"},{"issue":"pt A","key":"B60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mad.2016.06.004","article-title":"DNA damage in protective and adverse inflammatory responses: friend of foe?","volume":"165","author":"Poliezhaieva","year":"2017","journal-title":"Mech Ageing Dev"},{"key":"B61","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2013.00285","article-title":"Unsolved mysteries in NLR biology","volume":"4","author":"Lupfer","year":"2013","journal-title":"Front Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.05.002"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg219"},{"key":"B64","doi-asserted-by":"crossref","unstructured":"Ma Z, et al. Hes1 deficiency causes hematopoietic stem cell exhaustion [published online March 4, 2020]. Stem Cells. https:\/\/doi.org\/10.1002\/stem.3169","DOI":"10.1002\/stem.3169"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003389"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.8.2737.2737_2737_2744"},{"issue":"pt 9","key":"B67","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1242\/jcs.003152","article-title":"Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence","volume":"120","author":"Zhang","year":"2007","journal-title":"J Cell Sci"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5600"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.03.008"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.02.005"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-186684"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/133365\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:14:58Z","timestamp":1779192898000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/133365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,21]]},"references-count":71,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5,21]]},"published-print":{"date-parts":[[2020,5,21]]}},"alternative-id":["10.1172\/jci.insight.133365"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.133365","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,21]]},"article-number":"e133365"}}