Evidence map›Paper›PMID 42399991›Full record

ArticleJournal of translational medicine2026

Pilot spatial transcriptomics of dental pulpitis suggests immune-fibroblast profiling linked to reversibility.

Samer Zaky, Dhivyaa Rajasundaram, Alyssa Lu Lee, Kurt Summersgill, Steven Levine, Osama Boulos, Silvia Dunn, Giuseppe Intini, Charles Sfeir, Renato Silva

Abstract read
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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Samer ZakyDepartment of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA. shz33@pitt.edu.ORCID 0000-0001-5550-5450
Dhivyaa RajasundaramDepartment of Pediatrics, Division of Health Informatics, Children's Hospital of Pittsburgh, Pittsburgh, USA.
Alyssa Lu LeeInstitute for Quantitative Biomedicine, Rutgers University, Piscataway, New Jersey, USA.
Kurt SummersgillDepartment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Steven LevineDepartment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Osama BoulosDepartment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Silvia DunnDepartment of Diagnostic Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Giuseppe IntiniCenter for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Charles SfeirCenter for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA.
Renato SilvaDepartment of Endodontics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, USA. renato.silva@pitt.edu.

Funding

NIH HHS KL2TR001856 - 08S1
6 · The paper itself

Abstract

backgroundDiagnostic protocols in endodontics rely heavily on subjective pain assessments and sensibility testing, which may not reflect the underlying histopathological and molecular state of the dental pulp. This limitation can contribute to discordance between clinical diagnosis (reversible (RP) vs. irreversible (IP) pulpitis) and tissue biology, potentially leading to overtreatment of teeth that might respond to conservative, pulp-preserving approaches. Spatial transcriptomics offers an opportunity to explore the cellular and molecular heterogeneity of inflamed pulp in a spatially resolved manner.

objectiveTo explore spatial transcriptomic heterogeneity across healthy pulp and clinically diagnosed reversible and irreversible pulpitis samples, and to identify candidate immune-fibroblast features associated with an RP-like versus IP-like molecular profile.

methodsSpatial transcriptomics (Visium-CytAssist-V2) was performed on four human dental pulp tissues (n = 4). Cell deconvolution, differential gene expression, and pathway/module scoring were used to characterize spatial gene-expression patterns in healthy pulp and in clinically diagnosed RP and IP, with attention to coronal regions adjacent to carious lesions.

resultsDespite meeting clinical criteria for symptomatic IP, an IP sample exhibited spatial transcriptomic features more similar to the RP sample, including a comparable immune-to-fibroblast ratio and similar activation patterns of TLR4 and neuroinflammation-related pathways. Across clinically diagnosed IP samples, genes involved in immune signaling, cell migration, and tissue remodeling were differentially expressed. Increased PTN and CXCL14, together with lower expression of ENG (CD105), SELE, COL4A1, CXCL1, and CXCL13, emerged as candidate markers associated with an RP-like molecular profile in this pilot dataset. Overall, spatial patterns suggested that immune-fibroblast composition and interactions may contribute to transcriptomic differences across samples.

conclusionIn this hypothesis-generating pilot study, spatial transcriptomics highlighted substantial molecular heterogeneity within clinically diagnosed pulpitis and demonstrated that clinical labels may not consistently align with transcriptomic status. Candidate immune-fibroblast features identified here warrant validation in larger cohorts to determine the utility of spatial transcriptomics for refining pulpitis classification and guiding pulp-preserving treatment decisions.

Indexed as

FibroblastsPulpitisSpatial TranscriptomicsDental PulpFemaleGene Expression ProfilingGene Expression RegulationHumansMalePilot ProjectsFibroblastsMacrophagesPulpitisReversibility profileSpatial transcriptomics

Identifiers

PMID42399991
PMCPMC13340096

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