{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:29:00Z","timestamp":1791660540619,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR077435"],"award-info":[{"award-number":["R01AR077435"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AR077261"],"award-info":[{"award-number":["R21AR077261"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AR069619"],"award-info":[{"award-number":["P30AR069619"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01RX001321"],"award-info":[{"award-number":["I01RX001321"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell\u2010based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord\u2010derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte\u2010like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor\u2010beta\u00a0and phosphoinositide 3 kinase\u2010protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co\u2010localized with emerging glycosaminoglycan\u2010rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.<\/jats:p>","DOI":"10.1096\/fj.202301217r","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T19:39:18Z","timestamp":1702409958000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Single cell\n                    <scp>RNA<\/scp>\n                    sequencing reveals emergent\n                    <scp>notochord\u2010derived<\/scp>\n                    cell subpopulations in the postnatal nucleus pulposus"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-9236","authenticated-orcid":false,"given":"Chenghao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1153-4115","authenticated-orcid":false,"given":"Leilei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-7769","authenticated-orcid":false,"given":"Yian Khai","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0652-2075","authenticated-orcid":false,"given":"Lutian","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-8212","authenticated-orcid":false,"given":"Thomas P.","family":"Schaer","sequence":"additional","affiliation":[{"name":"Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine University of Pennsylvania  Kennett Square Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-603X","authenticated-orcid":false,"given":"Robert L.","family":"Mauck","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Translational Musculoskeletal Research Center Corporal Michael J. Crescenz Philadelphia VA Medical Center  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8839-9682","authenticated-orcid":false,"given":"Neil R.","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Neurosurgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2582-0078","authenticated-orcid":false,"given":"Ling","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5823-6073","authenticated-orcid":false,"given":"Lachlan J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Translational Musculoskeletal Research Center Corporal Michael J. Crescenz Philadelphia VA Medical Center  Philadelphia Pennsylvania USA"},{"name":"Department of Neurosurgery, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.16885"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken396"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60692-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1533-2500.2007.00171.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006403"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.4.SPINE14270"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199501000-00003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0000000000000328"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350652"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar629"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1036"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1043"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21805"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0284-x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008128"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01812"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000209302.00820.fd"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0021-8782.2004.00352.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e318166e001"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000253961.40910.c1"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpain.2022.894651"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X10666150113112149"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24408"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10692-5"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.08.006"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54695"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1074"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28952"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13254"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.780749"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1998.4287"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.08.027"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.05.005"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v022a22"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.02.027"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011189"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9941253"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(99)00049-9"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-007-0475-y"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1012508"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb44625.x"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2131"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1402720309"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206296"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2021.100082"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64940"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1683"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-5229fje"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02316"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0390563"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2019.118574"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI140214"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1815447116"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202301217R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T16:44:06Z","timestamp":1761669846000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202301217R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,12]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,15]]}},"alternative-id":["10.1096\/fj.202301217R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202301217r","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.21.541589","asserted-by":"object"}]},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,12]]},"assertion":[{"value":"2023-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23363"}}