Evidence map›Paper›PMID 41985508›Full record

ArticleCell proliferation2026

Single-Cell Virtual Perturbation Screening Identifies STAT3 as a Key Regulator of Dentinogenesis.

Yanfei Zhu, Hongyuan Xu, Zijian Zhang, Siyuan Sun, Zihan Huang, Xin Gao, Houwen Pan, Xiangru Huang, Yuanqi Liu, Xinyu Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell proliferation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Yanfei ZhuCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Hongyuan XuCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Zijian ZhangCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.ORCID https://orcid.org/0000-0002-9194-6314
Siyuan SunCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.ORCID https://orcid.org/0000-0003-0003-2830
Zihan HuangCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Xin GaoCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Houwen PanCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Xiangru HuangCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Yuanqi LiuCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Xinyu WangCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Hanbin JiaCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
Qinggang DaiThe 2nd Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.ORCID https://orcid.org/0000-0002-8177-2496
Lingyong JiangCenter of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.ORCID https://orcid.org/0000-0002-1624-4056

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dentine formation constitutes a physiological process precisely regulated by signal transduction modules governing odontoblast differentiation and mineralisation. First, by constructing a single-cell transcriptional landscape of odontogenic tissue, we defined EFNB2+ mesenchymal cells as a primary progenitor cluster, marking the origin of the odontogenic lineage. Integrating CellRank-based fate mapping and SCENIC-based regulon specificity analysis, we identified signal transducer and activator of transcription 3 (STAT3) as a pivotal transcriptional regulator of the odontoblast lineage. Subsequently, in silico perturbations using CellOracle predicted that STAT3 ablation disrupted the developmental vector field, redirecting the fate of mesenchymal precursors away from the odontoblast lineage. To substantiate these bioinformatic predictions, functional validation using shRNA-mediated silencing and pharmacological modulation demonstrated that STAT3 was essential for the proliferation and differentiation capacity of dental mesenchymal cells. Furthermore, we generated conditional knockout mice targeting Stat3 in Osterix-expressing odontoblast progenitors, which consequently exhibited significant dentine dysplasia. Mechanistically, RNA-seq and chromatin immunoprecipitation (ChIP) assays revealed that STAT3 directly bound to the WNT2B promoter, transcriptionally activating the Wnt/β-catenin signalling pathway in dental mesenchymal cells. Overexpression of WNT2B partially rescued the odontogenic defects induced by STAT3 inactivation. This 'prediction to verification' study establishes STAT3 as a critical regulator of dentinogenesis and provides potential therapeutic targets for the treatment of dentine developmental disorders and the advancement of dentine regeneration.

Indexed as

DentinogenesisSTAT3 Transcription FactorAnimalsCell DifferentiationCell ProliferationMesenchymal Stem CellsMiceMice, KnockoutOdontoblastsPromoter Regions, GeneticSingle-Cell AnalysisWnt ProteinsWnt Signaling PathwayStat3 protein, mouseSTAT3 Transcription FactorWnt Proteinsdentine developmentdentinogenesisin silico perturbationodontoblast differentiationSTAT3WNT2BWnt signalling pathway

Identifiers

PMID41985508
PMCPMC13325875

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.