Expression data from mouse calvarial suture mesenchymal cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74849 | GEO | 2015/11/11
SECONDARY ACCESSION(S): PRJNA301674
REPOSITORIES: GEO
Similar Datasets
Project description:Axin2-expressing calvarial suture stem cells can contribute to calvarial development, homeostatic maintenance, repair, and regeneration. We used microarray to examine the gene expression profiles of Axin2-expressing suture stem cells and Axin2-negative cells in suture mesenchyme. Three of Axin2+/GFP+ and three of Axin2-/GFP- cell samples were collected from mice carrying Axin2rtTA and TREH2BGFP transgenes. Each samples were isolated from 6-8 Axin2rtTA; TRE-H2BGFP mice and sorted by the GFP intensity.
2015-11-11 | E-GEOD-74849 | biostudies-arrayexpress
Project description:Craniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone and suture mesenchyme separates adjacent bones. We performed single-cell RNA-seq analysis of the embryonic, murine coronal suture. Seven populations at E16.5 and nine at E18.5 comprised the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog (HH) signaling, marked a mesenchymal population distinct from other neurocranial sutures. At E18.5, Hhip-/- coronal osteogenic fronts were closely apposed and HH signaling was increased throughout the depleted suture mesenchyme compared to WT, demonstrating that Hhip is required for normal coronal suture development. Tracing of the neonatal Hhip-expressing population showed that descendant cells persisted in the coronal suture and contributed to calvarial bone growth. Our transcriptomic approach provides a rich resource for insight into normal and abnormal development.
2021-06-26 | GSE178899 | GEO
Project description:The regeneration of craniofacial bones of the mammalian skeleton necessitates the action of both intrinsic and extrinsic inductive factors from multiple cell types, which function in a hierarchical and temporal fashion to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse cranial suture recently identified a suture mesenchymal progenitor population with tendon- or ligament-associated gene expression profile previously uncharacterized. Here, we developed a Mohawk homeobox (MkxCG;R26RtdT) reporter mouse, finding that this teno-ligamentous gene identifies a cranial suture resident cell population within the adult mouse that gives rise to calvarial osteoblasts and osteocytes overtime during homeostatic conditions. Single cell RNA-Sequencing (scRNA-Seq) demonstrated that Mkx+ suture cells demonstrate a stem-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 cranial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Furthermore, in vivo local deletion of Mkx in Mkx floxed mice resulted in robustly increased calvarial defect repair. Finally, we observed that mechanical stretch dynamically regulates Mkx expression in turn regulating calvarial cell osteogenesis. Overall, we identify Mkx+ cells within the suture mesenchyme as a progenitor cell population for adult craniofacial bones required for bone repair and Mkx itself as mechanical stretch responsive gene which functions to prevent osteogenic differentiation within the stem cell niche.
2024-06-13 | GSE245094 | GEO
Project description:The regeneration of craniofacial bones of the mammalian skeleton necessitates the action of both intrinsic and extrinsic inductive factors from multiple cell types, which function in a hierarchical and temporal fashion to control the differentiation of osteogenic progenitors. Single-cell transcriptomics of developing mouse cranial suture recently identified a suture mesenchymal progenitor population with tendon- or ligament-associated gene expression profile previously uncharacterized. Here, we developed a Mohawk homeobox (MkxCG;R26RtdT) reporter mouse, finding that this teno-ligamentous gene identifies a cranial suture resident cell population within the adult mouse that gives rise to calvarial osteoblasts and osteocytes overtime during homeostatic conditions. Single cell RNA-Sequencing (scRNA-Seq) demonstrated that Mkx+ suture cells demonstrate a stem-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 cranial suture cells, as knockdown or knockout resulted in increased osteogenic differentiation. Furthermore, in vivo local deletion of Mkx in Mkx floxed mice resulted in robustly increased calvarial defect repair. Finally, we observed that mechanical stretch dynamically regulates Mkx expression in turn regulating calvarial cell osteogenesis. Overall, we identify Mkx+ cells within the suture mesenchyme as a progenitor cell population for adult craniofacial bones required for bone repair and Mkx itself as mechanical stretch responsive gene which functions to prevent osteogenic differentiation within the stem cell niche.
2024-06-13 | GSE246238 | GEO
Project description:Purpose: The cranial suture is a fibrous joint, and similar to the growth plates of the skeletal long bone, they serve as the major centers of calvarial vault morphogenesis. Our group’s identification of a skeletal stem cell isolated from the mouse tibial growth plate prompted us to investigate whether these skeletal stem cells are also resident in the mouse cranial sutures and if they govern postnatal suture patency or fusion. Results: We preformed a spatio-temporal profiling of the mouse cranial sutures by flow cytometry, demonstrating a significant decrease in the temporal representation of skeletal stem cells in fusing versus patent sutures. Moreover, canonical Wnt signaling has a significant impact on skeletal stem cells proliferation and thus representation within the suture, dictating fate: fusion or patency. Breeding an Axin2+/-LacZ mouse, with enhanced activation of canonical Wnt signaling to a Twist1+/− mouse, harboring a coronal craniosynostosis enriched the skeletal stem cell pool in coronal sutures, thereby preventing Twist1+/− craniosynostosis. Conclusions: Our findings suggest an imbalance and/or decrease in resident skeletal stem cells within the cranial sutures gives rise to craniosynostosis, however, restoring this representation by enriching skeletal stem cells within the suture can maintain patency.
2020-04-15 | GSE138881 | GEO
Project description:Purpose: The cranial suture is a fibrous joint, and similar to the growth plates of the skeletal long bone, they serve as the major centers of calvarial vault morphogenesis. Our group’s identification of a skeletal stem cell isolated from the mouse tibial growth plate prompted us to investigate whether these skeletal stem cells are also resident in the mouse cranial sutures and if they govern postnatal suture patency or fusion. Results: We preformed a spatio-temporal profiling of the mouse cranial sutures by flow cytometry, demonstrating a significant decrease in the temporal representation of skeletal stem cells in fusing versus patent sutures. Moreover, canonical Wnt signaling has a significant impact on skeletal stem cells proliferation and thus representation within the suture, dictating fate: fusion or patency. Breeding an Axin2+/-LacZ mouse, with enhanced activation of canonical Wnt signaling to a Twist1+/− mouse, harboring a coronal craniosynostosis enriched the skeletal stem cell pool in coronal sutures, thereby preventing Twist1+/− craniosynostosis. Conclusions: Our findings suggest an imbalance and/or decrease in resident skeletal stem cells within the cranial sutures gives rise to craniosynostosis, however, restoring this representation by enriching skeletal stem cells within the suture can maintain patency.
2020-04-15 | GSE138880 | GEO
Project description:In newborn humans, and up to approximately 2 y of age, calvarial bone defects can naturally regenerate. This remarkable regeneration potential is also found in newborn mice and is absent in adult mice. Since previous studies showed that the mouse calvarial sutures are reservoirs of calvarial skeletal stem cells (cSSCs), which are the cells responsible for calvarial bone regeneration, here we hypothesized that the regenerative potential of the newborn mouse calvaria is due to a significant amount of cSSCs present in the newborn expanding sutures. Thus, we tested whether such regenerative potential can be reverse engineered in adult mice by artificially inducing an increase of the cSSCs resident within the adult calvarial sutures.First, we analyzed the cellular composition of the calvarial sutures in newborn and in older mice, up to 14-mo-old mice, showing that the sutures of the younger mice are enriched in cSSCs. Then, we demonstrated that a controlled mechanical expansion of the functionally closed sagittal sutures of adult mice induces a significant increase of the cSSCs. Finally, we showed that if a calvarial critical size bone defect is created simultaneously to the mechanical expansion of the sagittal suture, it fully regenerates without the need for additional therapeutic aids. Using a genetic blockade system, we further demonstrate that this endogenous regeneration is mediated by the canonical Wnt signaling.This study shows that controlled mechanical forces can harness the cSSCs and induce calvarial bone regeneration. Similar harnessing strategies may be used to develop novel and more effective bone regeneration autotherapies.
2023-04-11 | GSE227468 | GEO
Project description:Cranial sutures separate neighboring skull bones and contain skeletal stem cells that drive bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Here we integrate single-cell transcriptomics, in vivo expression validation, photoconversion-based lineage tracing, and a zebrafish craniosynostosis model to uncover key developmental transitions regulating bone formation during skull expansion. In addition to conservation of meninges and osteoblast lineage cells between zebrafish and mouse, single-cell transcriptomic analysis of the zebrafish skull reveals distinct subpopulations of suture mesenchyme that undergo transcriptomic changes during suture establishment. While lineage tracing with an osteoblast-specific nlsEOS reporter shows that bone formation largely occurs at suture edges, a subset of mesenchyme cells in the mid-suture region upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Further, lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. In twist1b; tcf12 mutant zebrafish, a model for the coronal synostosis of Saethre-Chotzen Syndrome, reduction of grem1a+ mid-suture cells correlates with misregulated bone formation and reduced blood vessels at the coronal suture. In addition, combinatorial mutation of BMP antagonists enriched in the mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data support roles of a subset of mid-suture mesenchyme in locally promoting BMP antagonism that ensures proper suture morphology.
2024-07-11 | GSE223147 | GEO
Project description:Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. In order to uncover the cellular diversity within sutures, we conducted single-cell transcriptomic and histological analyses of the embryonic murine coronal suture. We identify Erg and Pthlh as early markers of osteogenic progenitors in sutures, and distinct pre-osteoblast signatures between the bone fronts and periosteum. diverse mesenchymal layers at the coronal suture, including multiple distinct meningeal layers below the suture, and ligamentous, ectocranial, and hypodermal layers above the sutureIn the ectocranial layers above the suture, we observe a ligament-like population spanning the frontal and parietal bones and expressing genes implicated in mechanosensation. Mesenchyme in and around the coronal suture is asymmetrically distributed between the frontal and parietal bones, and we identify different states of osteogenic cells extending from the bone fronts into the more mature bone, and a potential signature for sutural stem cellsIn the meningeal layers, we detect a potential chondrogenic periosteal dura population that may be involved in endochondral ossification that closes sutures. Expression of genes mutated in craniosynostosis is spread across diverse cell types, suggesting multiple points at which homeostasis can fail. This single-cell atlas provides a resource to understand the development of the coronal suture, the suture most commonly fused in craniosynostosis.
2021-06-17 | GSE163693 | GEO
Project description:Expansion of the sagittal suture induces proliferation of skeletal stem cells and sustains endogenous calvarial bone regeneration
| PRJNA945322 | ENA