{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:11:15Z","timestamp":1781197875568,"version":"3.54.1"},"reference-count":81,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2021,12,25]],"date-time":"2021-12-25T00:00:00Z","timestamp":1640390400000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE025866"],"award-info":[{"award-number":["DE025866"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR070877"],"award-info":[{"award-number":["AR070877"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["CA222571"],"award-info":[{"award-number":["CA222571"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,6,29]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Understanding the cell origin and molecular mechanisms underlying rare genetic diseases provides invaluable insights into human biology and pathology of not only rare genetic diseases but also related common disorders. Autosomal dominant hyper immunoglobulin-E syndrome (AD-HIES) or Job syndrome is a genetic disease with skeletal defects resulting from mutations in the STAT3 gene. We have modeled the skeletal abnormality in Job Syndrome by deleting Stat3 using cell-specific Cre lines. We found that Stat3 is required in osteoblast lineage cells for skeletal development by maintaining Wnt\/\u03b2-catenin signaling. Deletion of\n                    <jats:italic>Stat3<\/jats:italic>\n                    resulted in impaired osteoblast differentiation due to reduced Wnt\/\u03b2-catenin signaling with upregulated\n                    <jats:italic>Sost<\/jats:italic>\n                    expression. Our work provides a foundation for further understanding the principles whereby\n                    <jats:italic>Stat3<\/jats:italic>\n                    governs bone formation and maintenance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2020100118","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T15:55:34Z","timestamp":1624636534000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["<i>Stat3<\/i>\n                    loss in mesenchymal progenitors causes Job syndrome\u2013like skeletal defects by reducing Wnt\/\u03b2-catenin signaling"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-5320","authenticated-orcid":false,"given":"Prem Swaroop","family":"Yadav","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-462X","authenticated-orcid":false,"given":"Hanjun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3933-887X","authenticated-orcid":false,"given":"Yingzi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115;"},{"name":"Harvard Stem Cell Institute, Cambridge, MA 02138"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"774","article-title":"Osteogenesis imperfecta tarda in a child with hyper-IgE syndrome","volume":"136","author":"Brestel E. P.","year":"1982","unstructured":"E. P. Brestel, W. G. Klingberg, R. W. Veltri, J. S. Dorn, Osteogenesis imperfecta tarda in a child with hyper-IgE syndrome. Am. J. Dis. Child. 136, 774\u2013776 (1982).","journal-title":"Am. J. Dis. Child."},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.156.2.4011897"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00441793"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903043400904"},{"key":"e_1_3_4_5_2","unstructured":"W. Hafsi S. N. S. Yarrarapu \u201cJob syndrome\u201d in StatPearls (StatPearls Publishing Treasure Island FL 2021)."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90106-M"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206479"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00963"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5332.1630"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215650"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073687"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515876112"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.059"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-602763"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06096"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3040"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000206"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.02.074"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.020"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006610"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/8792"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605170103"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.12.024"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111092198"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90057-9"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302703111"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004820"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237137100"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10092"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0989-6"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20892"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01461"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.06.001"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02480"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2019.100218"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.060810"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.G.01183"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52779"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2093-3"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/43206"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016071107"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201798873"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm979"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2006.08.004"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2388"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00130"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2514"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1485"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203548"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2017.01.008"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.07.024"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.6.1067"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1141"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.965702"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046892"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12102"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-1115"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2016.0212"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.074"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-4660"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006564"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.079129"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1159\/000016693"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.15.4261"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2013.177"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.185"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.12.042"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3067"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2467"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.02.015"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714313114"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22641"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-989-5_9"},{"key":"e_1_3_4_76_2","first-page":"66","article-title":"[Use of Masson\u2019s trichrome method for staining decalcified bone tissue]","volume":"58","author":"Asonova S. N.","year":"1996","unstructured":"S. N. Asonova, N. S. Migalkin, [Use of Masson\u2019s trichrome method for staining decalcified bone tissue]. Arkh. Patol. 58, 66\u201367 (1996).","journal-title":"Arkh. Patol."},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02623891"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts251"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2018.03.004"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-308171"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3314"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2020100118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2020100118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:58:00Z","timestamp":1649833080000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2020100118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":81,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2021,6,29]]}},"alternative-id":["10.1073\/pnas.2020100118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2020100118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]},"assertion":[{"value":"2021-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2020100118"}}