PT - JOURNAL ARTICLE AU - Yang, Xue AU - Han, Chuyi AU - Yu, Changhao AU - Zhou, Bin AU - Ye, Ling AU - Li, Feifei AU - Yu, Fanyuan TI - Inclusive, Exclusive and Hierarchical Atlas of NFATc1<sup>+</sup>/PDGFR-α<sup>+</sup> Cells in Dental and Periodontal Mesenchyme AID - 10.1101/2024.07.10.602887 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.07.10.602887 4099 - http://biorxiv.org/content/early/2024/10/01/2024.07.10.602887.short 4100 - http://biorxiv.org/content/early/2024/10/01/2024.07.10.602887.full AB - Platelet-derived growth factor receptor alpha (PDGFR-α) activity is crucial in the process of dental and periodontal mesenchyme regeneration facilitated by autologous platelet concentrates (APCs), such as platelet-rich fibrin (PRF), platelet-rich plasma (PRP) and concentrated growth factors (CGF), as well as by recombinant PDGF drugs. However, it is largely unclear about the physiological patterns and cellular fate determinations of PDGFR-α+ cells in the homeostasis maintaining of adult dental and periodontal mesenchyme. We previously identified NFATc1 expressing PDGFR-α+ cells as a subtype of skeletal stem cells (SSCs) in limb bone, but their roles in dental and periodontal remain unexplored. To this end, in the present study we investigated the spatiotemporal atlas of NFATc1+ and PDGFR-α+ cells residing in dental and periodontal mesenchyme, their capacity for progeny cell generation, and their inclusive, exclusive and hierarchical relations in homeostasis. We utilized CRISPR/Cas9-mediated gene editing to generate two dual recombination systems, which were Cre/loxP-Dre/Rox combined intersectional and exclusive reporters respectively, to concurrently demonstrate the inclusive, exclusive, and hierarchical distributions of NFATc1+ and PDGFR-α+ cells and their lineage commitment. By employing the state-of-the-art transgenic lineage tracing techniques in cooperating with tissue clearing-based advanced imaging and three-dimensional slices reconstruction, we systematically mapped the distribution atlas of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme and tracked their in vivo fate trajectories. Our findings extend current understanding of NFATc1+ and PDGFR-α+ cells in dental and periodontal mesenchyme homeostasis, and furthermore enhance our comprehension of their sustained therapeutic impact for future clinical investigations.Competing Interest StatementThe authors have declared no competing interest.