Plasticity within the niche ensures the maintenance of a <i>Sox2</i>+ stem cell population in the mouse incisor

Sanz-Navarro, Maria; Seidel, Kerstin; Sun, Zhao; Bertonnier-Brouty, Ludivine; Amendt, Brad A.; Klein, Ophir D.; Michon, Frédéric

doi:10.1242/dev.155929

Cited by 26 publications

(42 citation statements)

References 57 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed molecular heterogeneity may indicate the presence of several SC populations which each generate one or more tooth epithelial lineages; alternatively, the diverse molecular pattern may indicate a variety of stemness states of a single SC progeny. Our flow cytometry analysis demonstrated the diversity of Sox2-GFP+ SC population, in which some cells also express Ptch1, or, as recently reported, Lgr5 32 .…”

Section: Discussionsupporting

confidence: 87%

Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation

Binder

Biggs

Kronenberg

et al. 2020

Sci Rep

View full text Add to dashboard Cite

enamel is secreted by ameloblasts derived from tooth epithelial stem cells (Scs). Humans cannot repair or regenerate enamel, due to early loss of tooth epithelial Scs. contrarily in the mouse incisors, epithelial Scs are maintained throughout life and endlessly generate ameloblasts, and thus enamel. Here we isolated Sox2-GFP+ tooth epithelial Scs which generated highly cellular spheres following a novel in vitro strategy. this system enabled analysis of Sc regulation by various signaling molecules, and supported the stimulatory and inhibitory roles of Shh and Bmp, respectively; providing better insight into the heterogeneity of the Scs. further, we generated a novel mouse reporter, Enamelin-tdTomato for identification of ameloblasts in live tissues and cells, and used it to demonstrate presence of ameloblasts in the new 3D co-culture system of dental SCs. Collectively, our results provide means of generating 3D tooth epithelium from adult SCs which can be utilized toward future generation of enamel. Postnatally, stem cells (SC) remain within organ-specific SC niches and provide the source of reparative and regenerative potential. Continuously-growing rodent incisors contain epithelial and mesenchymal SC niches, which unceasingly produce the mineralized constituents of the adult tooth: enamel and dentin, respectively (reviewed in 1). The epithelial SCs reside in the labial cervical loops (LaCL) situated at the proximal end of the tooth, and are surrounded by their progeny, as well as the mesenchymal cells of dental pulp and follicle. Within the LaCL, these SCs are located in the loosely-arranged stellate reticulum and can be identified as slowly dividing, label-retaining cells, which express Sox2, Lgr5, Ptch1, Gli1, ABCG2, Bmi-1, and Oct3/4, among other genes 2-7. In vivo studies and in vitro explant cultures have demonstrated that the survival, proliferation, and differentiation of tooth epithelial SCs are regulated through complex, but not fully elucidated, interactions with the surrounding cells. An intricate signaling network involving several signaling pathways, including FGF, BMP, Activin, and Follistatin, regulates maintenance of SCs, transit-amplifying cell (TAC) proliferation, and ameloblast differentiation (reviewed in 8). In addition, we recently showed that functionally distinct Patched receptors establish multimodal Hedgehog signaling in the cervical loop 9 , which enables simultaneous regulation of maintenance of SCs and ameloblast differentiation, as previously reported 7,10. Published data have demonstrated that Fgf10 and Fgf3 positively regulate SCs, similar to Shh signaling, while BMP4 and mesenchyme-derived Wnt signaling have a negative effect on this population 10-12. Intriguingly, the incisor SC niche is characterized by exclusive lack of Wnt signaling, attributed to the enrichment of Wnt inhibitors 13. Epithelial SCs in mouse incisors continuously generate ameloblasts in a stepwise process during which the cells transit through increasing degrees of differentiation marked by the expression of...

show abstract

Section: Discussionsupporting

confidence: 87%

Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation

Binder

Biggs

Kronenberg

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…While no homolog of Lgr5 exists in teleost fishes, lgr4 was expressed in cichlid RT and TBs more similarly to that of sox2 , although more restricted to the basal layers of epithelium in and around the taste unit. This is an intriguing result, given that Lgr5 + cells replenish Sox2 + cells after genetic deletion of Sox2 in mouse incisors (8). igfbp5 , shown coincident in expression to lgr5 in gecko RT dental lamina (38), indeed colabels the basal epithelial cells associated with the regenerating RT–TB unit.…”

Section: Resultsmentioning

confidence: 89%

“…Classic work demonstrated that Sox2 marks the putative ESC niche in a cadre of mammals and reptiles (4), bony fishes (5), and sharks (1, 6). Genetic fate mapping experiments show that Sox2 + ESCs contribute to all lineages of the dental epithelium (7, 8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Developmental plasticity of epithelial stem cells in tooth and taste bud renewal

Bloomquist

Fowler

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In Lake Malawi cichlids, each tooth is replaced in one-for-one fashion every ∼20 to 50 d, and taste buds (TBs) are continuously renewed as in mammals. These structures are colocalized in the fish mouth and throat, from the point of initiation through adulthood. Here, we found that replacement teeth (RT) share a continuous band of epithelium with adjacent TBs and that both organs coexpress stem cell factors in subsets of label-retaining cells. We used RNA-seq to characterize transcriptomes of RT germs and TB-bearing oral epithelium. Analysis revealed differential usage of developmental pathways in RT compared to TB oral epithelia, as well as a repertoire of genome paralogues expressed complimentarily in each organ. Notably, BMP ligands were expressed in RT but excluded from TBs. Morphant fishes bathed in a BMP chemical antagonist exhibited RT with abrogated shh expression in the inner dental epithelium (IDE) and ectopic expression of calb2 (a TB marker) in these very cells. In the mouse, teeth are located on the jaw margin while TBs and other oral papillae are located on the tongue. Previous study reported that tongue intermolar eminence (IE) oral papillae of Follistatin (a BMP antagonist) mouse mutants exhibited dysmorphic invagination. We used these mutants to demonstrate altered transcriptomes and ectopic expression of dental markers in tongue IE. Our results suggest that vertebrate oral epithelium retains inherent plasticity to form tooth and taste-like cell types, mediated by BMP specification of progenitor cells. These findings indicate underappreciated epithelial cell populations with promising potential in bioengineering and dental therapeutics.

show abstract

“…Although the lineage tracing in this study clearly indicates that Sox2(+) cells contribute to the supernumerary tooth formation in GAG-deficient incisors, deleting Sox2 from Fam20B-deficient dental epithelium only partially rescued the phenotype. Sanz-Navarro et al [50] also observed mild tooth phenotypes when they removed Sox2 from Shh(+) population in the dental epithelium. They speculated that it may be related to the mosaic activation of Shh-Cre and/or redundancy from other Sox members.…”

Section: Discussionmentioning

confidence: 97%

FAM20B-catalyzed glycosaminoglycans control murine tooth number by restricting FGFR2b signaling

Tian

Han

et al. 2020

BMC Biol

View full text Add to dashboard Cite

Background: The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. Results: In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine tooth number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary tooth formation. Conclusions: The novel mechanism we have characterized through which GAGs control the tooth number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.

show abstract

Plasticity within the niche ensures the maintenance of a Sox2+ stem cell population in the mouse incisor

Cited by 26 publications

References 57 publications

Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation

Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation

Developmental plasticity of epithelial stem cells in tooth and taste bud renewal

FAM20B-catalyzed glycosaminoglycans control murine tooth number by restricting FGFR2b signaling

Contact Info

Product

Resources

About