{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:49:23Z","timestamp":1786978163459,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501845"],"award-info":[{"award-number":["81501845"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772432"],"award-info":[{"award-number":["81772432"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972035"],"award-info":[{"award-number":["81972035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Backgrounds<\/jats:title>\n                    <jats:p>Abnormal vertebral growth and development have been found in adolescent idiopathic scoliosis (AIS) patients, and the proliferation and differentiation of bone development\u2010related cells play important roles in its pathogenesis. However, a comprehensive single\u2010cell\u2010level differentiation roadmap in AIS has not been achieved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The present study compared the single\u2010cell level cellular landscapes of spinal cancellous bone tissues between AIS patients and healthy subjects using high throughput single\u2010cell RNA sequencing (scRNA\u2010seq), which covers multiple cellular lineages including osteoblast, chondrocyte, osteoclast and related immunocytes. We constructed the differentiation trajectories of bone development\u2010related cell lineages through pseudotime analysis, and the intercellular\u2010communication networks between bone development\u2010related cells and immunocytes were further developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 11 distinct cell clusters were identified according to the genome\u2010wide transcriptome profiles.\n                      <jats:italic>t<\/jats:italic>\n                      \u2010Distributed stochastic neighbor embedding (t\u2010SNE) analysis showed that mesenchymal stem cells (MSC) were classified into three subtypes: MSC\u2010LOXL2, MSC\u2010IGFBP5, and MSC\u2010GJA1. Gene ontology (GO) analysis showed that MSC\u2010GJA1 might possess greater osteoblast differentiation potential than the others. MSC\u2010IGFBP5 was the specific MSC subtype observed only in AIS. There were two distinct gene expression clusters: OB\u2010DPT and OB\u2010OLFML2B, and the counts of osteoblasts derived from AIS was significantly less than that of non\u2010AIS subjects. In AIS patients, MSC\u2010IGFBP5 failed to differentiate into osteoblasts and exhibited negative regulation of cell proliferation and enhanced cell death. CPC\u2010PCNA was found to be the specific chondrocyte progenitor cell (CPC) subtype observed only in AIS patients. The cell counts of OC\u2010BIRC3 in AIS were less than those in controls. Pseudotime analysis suggested two possible distinct osteoclast differentiation patterns in AIS and control subjects. Monocytes in AIS mainly differentiated into OC\u2010CRISP3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our single\u2010cell analysis first revealed differences existed in the cellular states between AIS patients and healthy subjects and found the differentiation disruption of specific MSC and CPC clusters in AIS. Cell communication analysis provided the possible pathogenesis of osteoblast and chondrocyte differentiation dysfunction in AIS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.1184","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T22:44:35Z","timestamp":1639003475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single\u2010cell\n                    <scp>RNA<\/scp>\n                    Seq reveals cellular l\n                    <scp>andscape\u2010specific<\/scp>\n                    characteristics and potential etiologies for adolescent idiopathic scoliosis"],"prefix":"10.1002","volume":"4","author":[{"given":"Yilin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5899-1009","authenticated-orcid":false,"given":"Mingyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Changhai Hospital, Navy Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center) Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Changhai Hospital, Navy Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Changhai Hospital, Navy Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Shanghai 10th People's Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Changhai Hospital, Navy Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinquan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopaedics, Xinhua Hospital Shanghai Jiaotong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Shanghai 10th People's Hospital Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.19342"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-008-0757-z"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11832-012-0457-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-017-2756-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181891751"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1315"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.029"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170976"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1426-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18323"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.109"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0716-x"},{"key":"e_1_2_8_14_1","article-title":"Isolation protocol of mouse monocyte\u2010derived dendritic cells and their subsequent in vitro activation with tumor immune complexes","volume":"135","author":"Santana\u2010Magal N","year":"2018","journal-title":"J Vis Exp"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2015.04.008"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-018-1640-6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.12.010"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212863"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2016.1183667"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.10.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.12.024"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3172"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05244-y"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2123"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2017.1341458"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.219"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11782-w"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0636-3"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5HI1117-454RR"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12599"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01388"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6549242"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah4573"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600672"},{"key":"e_1_2_8_35_1","article-title":"Pan\u2010myeloid differentiation of human cord blood derived CD34+ hematopoietic stem and progenitor cells","volume":"150","author":"Bapat A","year":"2019","journal-title":"J Vis Exp"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11386-4"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27575"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07316-5"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/1947603517725566"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-11-66"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21146-x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.4061\/2010\/830231"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-011812"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40814-017-0193-0"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22938"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1074-z"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700900"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6676"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01317"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0885"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.11.008"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioz091"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10677-0"},{"issue":"3","key":"e_1_2_8_54_1","first-page":"421","article-title":"Research of simulated microgravity regulate MC3T3\u2010E1 cells differentiation through the nuclear factor\u2010kappa B signaling pathway","volume":"36","author":"Han B","year":"2019","journal-title":"J Biomed Eng"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-016-4628-8"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.6b00783"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.256"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0874-3"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12212"},{"issue":"6","key":"e_1_2_8_60_1","first-page":"3181","article-title":"Hypoxia promotes maintenance of the chondrogenic phenotype in rat growth plate chondrocytes through the HIF\u20101alpha\/YAP signaling pathway","volume":"42","author":"Li H","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.03.019"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.216135"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12284"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0663-6"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-016-3132-4"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001394"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-017-1653-7"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.1184","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jsp2.1184","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.1184","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:25:18Z","timestamp":1693182318000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.1184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":66,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/jsp2.1184"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.1184","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-06-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1184"}}