Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation

Abstract

Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1 ’s function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.

Niches for Skeletal Stem Cells of Mesenchymal Origin

“…As described for various niches in which epithelial or hematopoietic stem cells reside, interplay between stem cells and their progeny is common ( Ferraro et al, 2010 ). Such interplay between mesenchymal cells is exemplified by the niche in the mouse incisor, where committed progeny signal back to the stem cells via interaction between delta like non-canonical Notch ligand 1 (Dlk1) and Notch ( Walker et al, 2019 ). In mouse articular cartilage Notch ligands and receptors are expressed in a distinct spatiotemporal pattern, with Notch1 being expressed by neonatal art-SSPCs ( Hayes et al, 2003 ; Dowthwaite et al, 2004 ).…”

“…The depletion of Notch signaling in the entire adult articular cartilage employing Aggrecan-CreERT transgenic mice results in progressive degeneration of the extracellular matrix, including loss of proteoglycan, along with fibrosis in the articular cartilage and altered chondrocyte morphology ( Liu et al, 2016 ). Thus, as in the mouse incisor ( Walker et al, 2019 ), the Notch signaling pathway may participate in regulating mouse art-SSPCs. At the same time, it is worth mentioning that Notch1 has been detected immunohistochemical in all zones of human articular cartilage ( Ustunel et al, 2008 ; Grogan et al, 2009 ) or, in one case, only during osteoarthritis ( Mahjoub et al, 2012 ), but that the existence of putative human art-SSPCs remains to be established.…”

Vitamin C alleviates the senescence of periodontal ligament stem cells through inhibition of Notch3 during long‐term culture

“…In PDL, Notch1 was related to PDL terminal development and completion, while Notch2 showed its privileges during the pre-occlusion stage preferentially (Denes et al, 2019). Additionally, Notch signaling also plays a vital part in regulating the differentiation and stemness maintenance of stem cells in many tissues (Cheung & Rando, 2013), including dental tissues, via different Notch receptors (Mitsiadis et al, 2017;Walker et al, 2019;C. Zhang, Chang, Sonoyama, Shi, & Wang, 2008).…”

“…In PDL, Notch1 was related to PDL terminal development and completion, while Notch2 showed its privileges during the pre‐occlusion stage preferentially (Denes et al, 2019). Additionally, Notch signaling also plays a vital part in regulating the differentiation and stemness maintenance of stem cells in many tissues (Cheung & Rando, 2013), including dental tissues, via different Notch receptors (Mitsiadis et al, 2017; Walker et al, 2019; C. Zhang, Chang, Sonoyama, Shi, & Wang, 2008). In PDLSCs, Notch signaling can participate in the osteogenic differentiation, induce osteoclastgenesis, and be involved in the neurogenic commitment as well (Nakao et al, 2009; Osathanon, Manokawinchoke, et al, 2013; Osathanon, Ritprajak, et al, 2013).…”

A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

“…Total RNA was extracted from fresh frozen tissue using the Qiazol ® reagent (Qiagen, UK), following the manufacturer's protocol. The quality and concentration of RNA was established using the NanoDrop 2000) Reverse transcription and real-time PCR was performed on 700 ng of total RNA as previously described [59]. Primers were designed against the reference coding sequence (CDS) for each gene ( Supplementary Table S3).…”