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The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells
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The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells
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Journal Article
The Mohawk homeobox gene represents a marker and osteo-inhibitory factor in calvarial suture osteoprogenitor cells
2024
Overview
The regeneration of the mammalian skeleton’s craniofacial bones necessitates the action of intrinsic and extrinsic inductive factors from multiple cell types, which function hierarchically and temporally to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse calvarial suture recently identified a suture mesenchymal progenitor population with previously unappreciated tendon- or ligament-associated gene expression profile. Here, we developed a Mohawk homeobox (
Mkx
CG
; R26R
tdT
) reporter mouse and demonstrated that this reporter identifies an adult calvarial suture resident cell population that gives rise to calvarial osteoblasts and osteocytes during homeostatic conditions. Single-cell RNA sequencing (scRNA-Seq) data reveal that
Mkx
+
suture cells display a progenitor-like phenotype with expression of teno-ligamentous genes. Bone injury with
Mkx
+
cell ablation showed delayed bone healing. Remarkably,
Mkx
gene played a critical role as an osteo-inhibitory factor in calvarial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Localized deletion of
Mkx
in vivo also resulted in robustly increased calvarial defect repair. We further showed that mechanical stretch dynamically regulates
Mkx
expression, in turn regulating calvarial cell osteogenesis. Together, we define
Mkx
+
cells within the suture mesenchyme as a progenitor population for adult craniofacial bone repair, and
Mkx
acts as a mechanoresponsive gene to prevent osteogenic differentiation within the stem cell niche.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
