{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:09:46Z","timestamp":1792613386189,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"NIH","award":["KL2TR001856 \u2013 08S1"],"award-info":[{"award-number":["KL2TR001856 \u2013 08S1"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08520-4","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:04:07Z","timestamp":1783083847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pilot spatial transcriptomics of dental pulpitis suggests immune-fibroblast profiling linked to reversibility"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-5450","authenticated-orcid":false,"given":"Samer","family":"Zaky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhivyaa","family":"Rajasundaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa Lu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Summersgill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Boulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Intini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Sfeir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"issue":"Suppl 2","key":"8520_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/iej.13866","volume":"56","author":"HF Duncan","year":"2023","unstructured":"Duncan HF, El-Karim I, Dummer PMH, Whitworth J, Nagendrababu V. Factors that influence the outcome of pulpotomy in permanent teeth. Int Endod J. 2023;56(Suppl 2):62\u201381.","journal-title":"Int Endod J"},{"issue":"9","key":"8520_CR2","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1111\/iej.12793","volume":"50","author":"WJ Wolters","year":"2017","unstructured":"Wolters WJ, Duncan HF, Tomson PL, Karim IE, McKenna G, Dorri M, et al. Minimally invasive endodontics: a new diagnostic system for assessing pulpitis and subsequent treatment needs. Int Endod J. 2017;50(9):825\u20139.","journal-title":"Int Endod J"},{"key":"8520_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.4103\/1735-3327.340110","volume":"19","author":"M Raoof","year":"2022","unstructured":"Raoof M, Vazavandi E, Parizi MT, Hatami N, Mohammadalizadeh S, Amanpour S, Haghani J. Clinical, radiological, and histological correlation in diagnosis of pulpitis. Dent Res J (Isfahan). 2022;19:25.","journal-title":"Dent Res J (Isfahan)"},{"issue":"9","key":"8520_CR4","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1016\/j.jdent.2014.06.012","volume":"42","author":"D Ricucci","year":"2014","unstructured":"Ricucci D, Loghin S, Lin LM, Spangberg LS, Tay FR. Is hard tissue formation in the dental pulp after the death of the primary odontoblasts a regenerative or a reparative process? J Dent. 2014;42(9):1156\u201370.","journal-title":"J Dent"},{"key":"8520_CR5","doi-asserted-by":"crossref","unstructured":"El Karim IA. Deciphering reparative processes in the inflamed dental pulp. Front Dent Med. 2021;2.","DOI":"10.3389\/fdmed.2021.651219"},{"key":"8520_CR6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jdent.2019.05.022","volume":"86","author":"D Ricucci","year":"2019","unstructured":"Ricucci D, Siqueira JF Jr., Li Y, Tay FR. Vital pulp therapy: histopathology and histobacteriology-based guidelines to treat teeth with deep caries and pulp exposure. J Dent. 2019;86:41\u201352.","journal-title":"J Dent"},{"key":"8520_CR7","doi-asserted-by":"crossref","unstructured":"Tosco V, Monterubbianesi R, Montagna P, Orilisi G, Vitiello F, Song H, et al. Vital pulp therapy: a three-year clinical case series on regenerative potential and adhesive restoration strategies. Regenesis Repair Rehabilitation. 2026.","DOI":"10.1016\/j.rerere.2026.01.005"},{"key":"8520_CR8","doi-asserted-by":"publisher","first-page":"1474466","DOI":"10.3389\/fimmu.2024.1474466","volume":"15","author":"S Pohl","year":"2024","unstructured":"Pohl S, Akamp T, Smeda M, Uderhardt S, Besold D, Krastl G, et al. Understanding dental pulp inflammation: from signaling to structure. Front Immunol. 2024;15:1474466.","journal-title":"Front Immunol"},{"issue":"11","key":"8520_CR9","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1016\/j.joen.2023.08.013","volume":"49","author":"D Abraham","year":"2023","unstructured":"Abraham D, Singh A, Goyal A. Symptomatic Irreversible Pulpitis Induces Increased Levels of Human NLRP3 in Gingival Crevicular Fluid Compared to Saliva: A Case Control Observational Study. J Endod. 2023;49(11):1480\u20136.","journal-title":"J Endod"},{"issue":"10","key":"8520_CR10","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1016\/j.joen.2020.07.013","volume":"46","author":"G Akbal Dincer","year":"2020","unstructured":"Akbal Dincer G, Erdemir A, Kisa U, Comparison of Neurokinin A, Substance P. Interleukin 8, and Matrix Metalloproteinase-8 Changes in Pulp tissue and Gingival Crevicular Fluid Samples of Healthy and Symptomatic Irreversible Pulpitis Teeth. J Endod. 2020;46(10):1428\u201337.","journal-title":"J Endod"},{"issue":"7","key":"8520_CR11","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.joen.2023.05.002","volume":"49","author":"HN Cho","year":"2023","unstructured":"Cho HN, Chaves de Souza L, Johnson C, Klein JR, Kirkpatrick TC, Silva R, Letra A. Differentially Expressed Genes in Dental Pulp Tissues of Individuals With Symptomatic Irreversible Pulpitis With and Without History of COVID-19. J Endod. 2023;49(7):799\u2013807.","journal-title":"J Endod"},{"issue":"1","key":"8520_CR12","doi-asserted-by":"publisher","first-page":"4816","DOI":"10.1038\/s41467-020-18512-7","volume":"11","author":"J Krivanek","year":"2020","unstructured":"Krivanek J, Soldatov RA, Kastriti ME, Chontorotzea T, Herdina AN, Petersen J, et al. Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth. Nat Commun. 2020;11(1):4816.","journal-title":"Nat Commun"},{"key":"8520_CR13","doi-asserted-by":"crossref","unstructured":"Opasawatchai Aea. Single-cell transcriptomic profiling of human dental pulp in sound and carious teeth: a pilot study. Front Dent Med. 2022.","DOI":"10.3389\/fdmed.2021.806294"},{"issue":"1","key":"8520_CR14","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1177\/00220345231205283","volume":"103","author":"Y Yang","year":"2024","unstructured":"Yang Y, Alves T, Miao MZ, Wu YC, Li G, Lou J, et al. Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells. J Dent Res. 2024;103(1):71\u201380.","journal-title":"J Dent Res"},{"issue":"4","key":"8520_CR15","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41587-021-00830-w","volume":"40","author":"DM Cable","year":"2022","unstructured":"Cable DM, Murray E, Zou LS, Goeva A, Macosko EZ, Chen F, Irizarry RA. Robust decomposition of cell type mixtures in spatial transcriptomics. Nat Biotechnol. 2022;40(4):517\u201326.","journal-title":"Nat Biotechnol"},{"issue":"9S","key":"8520_CR16","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1016\/j.joen.2020.06.029","volume":"46","author":"C Le Fournis","year":"2020","unstructured":"Le Fournis C, Jeanneau C, Roumani S, Giraud T, About I. Pulp Fibroblast Contribution to the Local Control of Pulp Inflammation via Complement Activation. J Endod. 2020;46(9S):S26\u201332.","journal-title":"J Endod"},{"issue":"8","key":"8520_CR17","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1111\/iej.12511","volume":"49","author":"CV Machado","year":"2016","unstructured":"Machado CV, Passos ST, Campos TM, Bernardi L, Vilas-Boas DS, Nor JE, et al. The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression. Int Endod J. 2016;49(8):755\u201363.","journal-title":"Int Endod J"},{"key":"8520_CR18","doi-asserted-by":"publisher","first-page":"e112","DOI":"10.1590\/1807-3107bor-2017.vol31.0112","volume":"31","author":"Y Yan","year":"2017","unstructured":"Yan Y, Qi S, Gong SQ, Shang G, Zhao Y. Effect of CRABP2 on the proliferation and odontoblastic differentiation of hDPSCs. Braz Oral Res. 2017;31:e112.","journal-title":"Braz Oral Res"},{"issue":"3","key":"8520_CR19","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.bcp.2015.03.001","volume":"95","author":"SL Arnold","year":"2015","unstructured":"Arnold SL, Kent T, Hogarth CA, Griswold MD, Amory JK, Isoherranen N. Pharmacological inhibition of ALDH1A in mice decreases all-trans retinoic acid concentrations in a tissue specific manner. Biochem Pharmacol. 2015;95(3):177\u201392.","journal-title":"Biochem Pharmacol"},{"issue":"6","key":"8520_CR20","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.3324\/haematol.2019.243543","volume":"105","author":"G Pavlasova","year":"2020","unstructured":"Pavlasova G, Mraz M. The regulation and function of CD20: an enigma of B-cell biology and targeted therapy. Haematologica. 2020;105(6):1494\u2013506.","journal-title":"Haematologica"},{"issue":"11","key":"8520_CR21","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1111\/j.1365-2591.2010.01757.x","volume":"43","author":"KF Bruno","year":"2010","unstructured":"Bruno KF, Silva JA, Silva TA, Batista AC, Alencar AH, Estrela C. Characterization of inflammatory cell infiltrate in human dental pulpitis. Int Endod J. 2010;43(11):1013\u201321.","journal-title":"Int Endod J"},{"issue":"2","key":"8520_CR22","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.phrs.2008.05.013","volume":"58","author":"M Goldberg","year":"2008","unstructured":"Goldberg M, Farges JC, Lacerda-Pinheiro S, Six N, Jegat N, Decup F, et al. Inflammatory and immunological aspects of dental pulp repair. Pharmacol Res. 2008;58(2):137\u201347.","journal-title":"Pharmacol Res"},{"issue":"9","key":"8520_CR23","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1093\/intimm\/dxl070","volume":"18","author":"J Zhang","year":"2006","unstructured":"Zhang J, Kawashima N, Suda H, Nakano Y, Takano Y, Azuma M. The existence of CD11c+ sentinel and F4\/80\u2009+\u2009interstitial dendritic cells in dental pulp and their dynamics and functional properties. Int Immunol. 2006;18(9):1375\u201384.","journal-title":"Int Immunol"},{"issue":"2","key":"8520_CR24","doi-asserted-by":"publisher","first-page":"149","DOI":"10.5603\/FHC.2013.0023","volume":"51","author":"JM Tomaszewska","year":"2013","unstructured":"Tomaszewska JM, Miskowiak B, Matthews-Brzozowska T, Wierzbicki P. Characteristics of dental pulp in human upper first premolar teeth based on immunohistochemical and morphometric examinations. Folia Histochem Cytobiol. 2013;51(2):149\u201355.","journal-title":"Folia Histochem Cytobiol"},{"key":"8520_CR25","doi-asserted-by":"crossref","unstructured":"Beenen AC, Sauerer T, Schaft N, D\u00f6rrie J. Beyond cancer: regulation and function of PD-L1 in health and immune-related diseases. Int J Mol Sci. 2022;23(15).","DOI":"10.3390\/ijms23158599"},{"issue":"1","key":"8520_CR26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41368-022-00168-2","volume":"14","author":"SM Jeon","year":"2022","unstructured":"Jeon SM, Lim JS, Park SH, Kim HJ, Kim HR, Lee JH. Blockade of PD-L1\/PD-1 signaling promotes osteo-\/odontogenic differentiation through Ras activation. Int J Oral Sci. 2022;14(1):18.","journal-title":"Int J Oral Sci"},{"key":"8520_CR27","doi-asserted-by":"publisher","first-page":"184","DOI":"10.22203\/eCM.v041a13","volume":"41","author":"SH Zaky","year":"2021","unstructured":"Zaky SH, Shehabeldin M, Ray H, Sfeir C. The role of inflammation modulation in dental pulp regeneration. Eur Cell Mater. 2021;41:184\u201393.","journal-title":"Eur Cell Mater"},{"key":"8520_CR28","doi-asserted-by":"publisher","first-page":"119228","DOI":"10.1016\/j.gep.2021.119228","volume":"43","author":"D Bayarsaihan","year":"2022","unstructured":"Bayarsaihan D, Enkhmandakh B, Vijaykumar A, Robson P, Mina M. Single-cell transcriptome analysis defines mesenchymal stromal cells in the mouse incisor dental pulp. Gene Expr Patterns. 2022;43:119228.","journal-title":"Gene Expr Patterns"},{"issue":"1","key":"8520_CR29","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s12864-023-09265-w","volume":"24","author":"N Jiravejchakul","year":"2023","unstructured":"Jiravejchakul N, Abe GL, Loza M, Park S, Matangkasombut P, Sasaki JI, et al. Intercellular crosstalk in adult dental pulp is mediated by heparin-binding growth factors Pleiotrophin and Midkine. BMC Genomics. 2023;24(1):184.","journal-title":"BMC Genomics"},{"issue":"3","key":"8520_CR30","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1097\/00004770-200003000-00012","volume":"26","author":"IB Bender","year":"2000","unstructured":"Bender IB. Pulpal pain diagnosis\u2013a review. J Endod. 2000;26(3):175\u20139.","journal-title":"J Endod"},{"issue":"4","key":"8520_CR31","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/gene.2016.14","volume":"17","author":"JC Galicia","year":"2016","unstructured":"Galicia JC, Henson BR, Parker JS, Khan AA. Gene expression profile of pulpitis. Genes Immun. 2016;17(4):239\u201343.","journal-title":"Genes Immun"},{"issue":"2","key":"8520_CR32","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.joen.2010.10.009","volume":"37","author":"TW Lovelace","year":"2011","unstructured":"Lovelace TW, Henry MA, Hargreaves KM, Diogenes A. Evaluation of the delivery of mesenchymal stem cells into the root canal space of necrotic immature teeth after clinical regenerative endodontic procedure. J Endod. 2011;37(2):133\u20138.","journal-title":"J Endod"},{"key":"8520_CR33","doi-asserted-by":"publisher","first-page":"1808361","DOI":"10.1155\/2021\/1808361","volume":"2021","author":"B Xin","year":"2021","unstructured":"Xin B, Lin Y, Tian H, Song J, Zhang L, Lv J. Identification of Pulpitis-Related Potential Biomarkers Using Bioinformatics Approach. Comput Math Methods Med. 2021;2021:1808361.","journal-title":"Comput Math Methods Med"},{"issue":"11","key":"8520_CR34","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.joen.2008.07.023","volume":"34","author":"HW Jiang","year":"2008","unstructured":"Jiang HW, Ling JQ, Gong QM. The expression of stromal cell-derived factor 1 (SDF-1) in inflamed human dental pulp. J Endod. 2008;34(11):1351\u20134.","journal-title":"J Endod"},{"key":"8520_CR35","doi-asserted-by":"publisher","first-page":"593653","DOI":"10.3389\/fcell.2020.593653","volume":"8","author":"Y Liu","year":"2020","unstructured":"Liu Y, Zhang Z, Li W, Tian S. PECAM1 Combines With CXCR4 to Trigger Inflammatory Cell Infiltration and Pulpitis Progression Through Activating the NF-kappaB Signaling Pathway. Front Cell Dev Biol. 2020;8:593653.","journal-title":"Front Cell Dev Biol"},{"issue":"8","key":"8520_CR36","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.joen.2022.05.004","volume":"48","author":"JL Alvarez-Vasquez","year":"2022","unstructured":"Alvarez-Vasquez JL, Castaneda-Alvarado CP. Dental Pulp Fibroblast: A Star Cell. J Endod. 2022;48(8):1005\u201319.","journal-title":"J Endod"},{"issue":"9","key":"8520_CR37","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1016\/j.joen.2015.04.006","volume":"41","author":"JY Liu","year":"2015","unstructured":"Liu JY, Chen X, Yue L, Huang GT, Zou XY. CXC Chemokine Receptor 4 Is Expressed Paravascularly in Apical Papilla and Coordinates with Stromal Cell-derived Factor-1alpha during Transmigration of Stem Cells from Apical Papilla. J Endod. 2015;41(9):1430\u20136.","journal-title":"J Endod"},{"key":"8520_CR38","doi-asserted-by":"crossref","unstructured":"Liu L, Wang J, Yu J, Wang J, Yu J. ATF3 triggers M2 macrophage polarization to protect against pulp inflammation through WNT4 regulation. Acta Biochim Biophys Sin (Shanghai). 2025.","DOI":"10.3724\/abbs.2025005"},{"issue":"9","key":"8520_CR39","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1016\/j.joen.2021.06.015","volume":"47","author":"C Le Fournis","year":"2021","unstructured":"Le Fournis C, Jeanneau C, Giraud T, El Karim I, Lundy FT, About I. Fibroblasts Control Macrophage Differentiation during Pulp Inflammation. J Endod. 2021;47(9):1427\u201334.","journal-title":"J Endod"},{"issue":"7","key":"8520_CR40","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.1128\/IAI.72.7.4102-4108.2004","volume":"72","author":"JL McLachlan","year":"2004","unstructured":"McLachlan JL, Sloan AJ, Smith AJ, Landini G, Cooper PR. S100 and cytokine expression in caries. Infect Immun. 2004;72(7):4102\u20138.","journal-title":"Infect Immun"},{"key":"8520_CR41","doi-asserted-by":"publisher","first-page":"104695","DOI":"10.1016\/j.jdent.2023.104695","volume":"138","author":"H Sun","year":"2023","unstructured":"Sun H, Meng S, Xu Z, Cai H, Pei X, Wan Q, Chen J. Vascular and lymphatic heterogeneity and age-related variations of dental pulps. J Dent. 2023;138:104695.","journal-title":"J Dent"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08520-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08520-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08520-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:36:45Z","timestamp":1783348605000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08520-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8520"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08520-4","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"assertion":[{"value":"27 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Data presented in this study come from four dental pulp samples collected from four adult subjects recruited through the University of Pittsburgh School of Dental Medicine\u2019s Emergency and Oral and Craniofacial Surgery clinics. All participants enrolled in this study provided a written informed consent under Institutional Review Board (IRB) Protocol #23050001 at the University of Pittsburgh.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"857"}}