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Decoding SFRP2hi Fibroblast Progenitors in Sustaining Tooth Growth in Humans and Mice at Single-Cell Resolution

ABSTRACT: Single-cell transcriptomics has revolutionized tooth biology by uncovering previously unexplored areas. The mouse is a widely used model for studying human tissues and diseases, including dental pulp tissues. While human and mouse molars share many similarities, mouse incisors differ significantly from human teeth due to their continuous growth throughout their lifespan. The extent to which studies on mouse teeth can be applied to human disease translation remains underexplored. By leveraging multiple single-cell datasets, we constructed a comprehensive dental pulp cell landscape to clarify tissue similarities and species-specific differences between humans and mice. Notably, we identified a distinct cell population, Sfrp2hi fibroblast progenitors, found exclusively in mouse incisors and the developing tooth root of human molars. These cells are uniquely present to sustain continuous tissue growth. Mechanistically, we found that the transcription factor Twist1, regulated by MAPK phosphorylation, binds to the Sfrp2 promoter and modulates Wnt signaling activation to maintain stem cell identities. Our research reveals a previously unrecognized subset of dental mesenchymal stem cells instrumental in tooth growth. This distinct subset is evolutionarily conserved in both humans and mice, offering valuable translational insights.

ORGANISM(S): Mus musculus

PROVIDER: GSE275119 | GEO | 2025/02/12

REPOSITORIES: GEO

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Project description:The dentition of elasmobranchs (sharks, skates and rays) is uniquely productive, capable of both rapid and continuous, lifelong regeneration. Elasmobranchs represent an important group of vertebrates with a deep evolutionary history, possessing several ancient and basal characters, i.e., the continuously regenerative dentition from a specialized dental lamina. The dental lamina is an expanded component of the oral epithelia that is responsible for initiating and producing new teeth among all toothed-vertebrates. In sharks, this dynamic epithelial unit is permanent and continuous – meaning it extends to cover the entirety of each jaw (jaw-wide) and develops early during embryogenesis and retained to produce teeth for the life of the shark. It is rare for a truly embryonic vertebrate tissue to be retained for its original function for the life of the organism. The dental lamina in sharks is unique and houses teeth in a developmental series from the deepest part, where teeth are initiated, through stages of tooth development in the form of a related, family of teeth to eruption and functionality of the advanced teeth at the jaw margin. How teeth are made and regenerated is an important question in vertebrate biology; here we investigated this question in the small spotted catshark (Scyliorhinus canicula), a new model in the field of developmental biology. Specifically, we divided the shark dental lamina into stage-compartments as follows: (i) the initiation site – the successional lamina (SL); (ii) the early developing teeth (ET); (iii) the late stage developing teeth (LT); (iv) the tooth-taste junction between the superficial oral and dental epithelium at the jaw margin that separates the taste territory and the dental lamina proper (TTJ); and basi-hyal oral epithelium that is strictly non-dental and only contains taste buds (BHTB). These 5 compartments each house both a shared and unique signature of gene transcripts. This study aims to understand the transcriptomic basis of continuous tooth regeneration in the shark. In this study we combine X-ray computed tomography, classic histology, insitu hybridization, immunohistochemistry, and functional assays of novel markers, and de novo and genome guided transcriptome assemblies for each of these 5 dental lamina compartments of the hatchling (stage 34) catshark (S. canicula).

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Decoding SFRP2hi Fibroblast Progenitors in Sustaining Tooth Growth in Humans and Mice at Single-Cell Resolution

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