Single-cell RNA sequencing reveals vascularization-associated cell subpopulations in dental pulp: PDGFRβ+ DPSCs with activated PI3K/AKT pathway.

Stem Cells

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.

Published: October 2024

AI Article Synopsis

  • This study aims to improve dental pulp regeneration therapy by addressing challenges related to the variety of Dental Pulp Stem Cells (DPSCs) from different donors and conditions.
  • Researchers used pseudotime analysis and flow cytometry to identify a specific subset of DPSCs known as PDGFRβ+ DPSCs, which showed high expression of fibronectin 1 (FN1) and strong abilities to promote blood vessel formation.
  • The findings suggest that PDGFRβ+ DPSCs are crucial for dental pulp development and have significant potential for clinical applications in regenerative medicine due to their robust proliferative and pro-angiogenic properties.

Article Abstract

Background: This study aims to address challenges in dental pulp regeneration therapy. The heterogeneity of DPSCs poses challenges, especially in stem cell transplantation for clinical use, particularly when sourced from donors of different ages and conditions.

Methods: Pseudotime analysis was employed to analyze single-cell sequencing data, and immunohistochemical studies were conducted to investigate the expression of fibronectin 1 (FN1). We performed in vitro sorting of PDGFRβ+ DPSCs using flow cytometry. A series of functional assays, including cell proliferation, scratch, and tube formation assays, were performed to experimentally validate the vasculogenic capabilities of the identified PDGFRβ+ DPSC subset. Furthermore, gene-edited mouse models were utilized to demonstrate the importance of PDGFRβ+ DPSCs. Transcriptomic sequencing was conducted to compare the differences between PDGFRβ+ DPSCs and P1-DPSCs.

Results: Single-cell sequencing analysis unveiled a distinct subset, PDGFRβ+ DPSCs, characterized by significantly elevated FN1 expression during dental pulp development. Subsequent cell experiments demonstrated that this subset possesses remarkable abilities to promote HUVEC proliferation, migration, and tube formation. Gene-edited mouse models confirmed the vital role of PDGFRβ+ DPSCs in dental pulp development. Transcriptomic sequencing and in vitro experiments demonstrated that the PDGFR/PI3K/AKT signaling pathway is a crucial factor mediating the proliferation rate and pro-angiogenic properties of PDGFRβ+ DPSCs.

Conclusion: We defined a new subset, PDGFRβ+ DPSCs, characterized by strong proliferative activity and pro-angiogenic capabilities, demonstrating significant clinical translational potential.

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Source
http://dx.doi.org/10.1093/stmcls/sxae051DOI Listing

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