Autocrine ECM molecules establish MSC quiescence during incisor development by disrupting WNT ligand trafficking process.
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| Titel: | Autocrine ECM molecules establish MSC quiescence during incisor development by disrupting WNT ligand trafficking process. |
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| Autoren: | Chen Z; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.; Chinese Institute for Brain Research, Beijing, China., Cai M; Chinese Institute for Brain Research, Beijing, China.; Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China., Wang Y; Chinese Institute for Brain Research, Beijing, China., Li X; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China., He Y; Qujing Medical College, Qujing City, Yunnan Province, China., Pu H; Qujing Medical College, Qujing City, Yunnan Province, China., Huang J; Chinese Institute for Brain Research, Beijing, China., Ye L; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China., Yang R; Department of Orthodontics, Peking University School and Hospital of Stomatology, National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China. ruiliyang@bjmu.edu.cn., Jing J; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China. junjunjing@scu.edu.cn., Zhao H; Chinese Institute for Brain Research, Beijing, China. zhaohu@cibr.ac.cn. |
| Quelle: | Nature communications [Nat Commun] 2025 Nov 27; Vol. 16 (1), pp. 10676. Date of Electronic Publication: 2025 Nov 27. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH-Schlagworte: | Mesenchymal Stem Cells*/metabolism , Mesenchymal Stem Cells*/cytology , Incisor*/cytology , Incisor*/metabolism , Incisor*/embryology , Incisor*/growth & development , Extracellular Matrix*/metabolism , Wnt Proteins*/metabolism , Autocrine Communication*, Animals ; Mice ; Ligands ; Wnt Signaling Pathway ; Dental Pulp/cytology ; Dental Pulp/metabolism ; Glypicans/metabolism ; Dental Papilla/metabolism ; Dental Papilla/cytology ; Odontogenesis ; Female ; Male ; Receptors, G-Protein-Coupled |
| Abstract: | Competing Interests: Competing interests: The authors declare no competing interests. Stem cells support homeostasis and injury repair of adult organs. It remains unclear when and how adult stem cells form during development. Here, we discover that incisor mesenchymal stem cells, marked by an extracellular matrix molecule Smoc2, establish their identity and quiescence between E14.5 and E16.5, and persist into adulthood. They support both embryonic tooth development and postnatal organ turnover. Concurrently, the incisor mesenchyme evolves from a homogenous dental papilla into a heterogeneous dental pulp consisting of a complete lineage hierarchy, which persists into adulthood. Smoc2 and its homologous molecule Smoc1 are indispensable for maintaining the quiescence and hierarchy of mesenchymal stem cells. They function by disrupting the binding between canonical WNT ligands and glypican, a process critical for transporting hydrophobic WNT ligands within the aqueous niche. In conclusion, mesenchymal stem cells establish their quiescence during development through autocrine extracellular matrix molecules to keep canonical WNT ligands from accessing them. (© 2025. The Author(s).) |
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| Substance Nomenclature: | 0 (Wnt Proteins) 0 (Ligands) 0 (Glypicans) 0 (Gpr177 protein, mouse) 0 (Receptors, G-Protein-Coupled) |
| Entry Date(s): | Date Created: 20251127 Date Completed: 20251127 Latest Revision: 20251130 |
| Update Code: | 20251130 |
| PubMed Central ID: | PMC12660891 |
| DOI: | 10.1038/s41467-025-65705-z |
| PMID: | 41309624 |
| Datenbank: | MEDLINE |
| Abstract: | Competing Interests: Competing interests: The authors declare no competing interests.<br />Stem cells support homeostasis and injury repair of adult organs. It remains unclear when and how adult stem cells form during development. Here, we discover that incisor mesenchymal stem cells, marked by an extracellular matrix molecule Smoc2, establish their identity and quiescence between E14.5 and E16.5, and persist into adulthood. They support both embryonic tooth development and postnatal organ turnover. Concurrently, the incisor mesenchyme evolves from a homogenous dental papilla into a heterogeneous dental pulp consisting of a complete lineage hierarchy, which persists into adulthood. Smoc2 and its homologous molecule Smoc1 are indispensable for maintaining the quiescence and hierarchy of mesenchymal stem cells. They function by disrupting the binding between canonical WNT ligands and glypican, a process critical for transporting hydrophobic WNT ligands within the aqueous niche. In conclusion, mesenchymal stem cells establish their quiescence during development through autocrine extracellular matrix molecules to keep canonical WNT ligands from accessing them.<br /> (© 2025. The Author(s).) |
|---|---|
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-025-65705-z |
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