Twist1-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-derived Parietal Bone through Downregulation of Fgf23
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE119962 | GEO | 2018/09/15
REPOSITORIES: GEO
Similar Datasets
Project description:Twist1-Haploinsufficiency Selectively Enhances the Osteoskeletal Capacity of Mesoderm-derived Parietal Bone through Downregulation of Fgf23
| PRJNA490833 | ENA
Project description:Certain bone graft materials are employed for alveolar bone regeneration, and autografts are commonly used. Alveolar and jaw bones are developmentally derived from neural crest cells, while most trunk and limb bones are derived from mesodermal mesenchymal cells. Consequently, the chosen bone graft material is likely to have a different developmental origin than the recipient bone. We hypothesized that there are differences in the gene expression profiles and bone healing capacities between bones with different developmental origins. Therefore, we investigated these properties in the maxilla, mandible, ilium and femur. DNA microarray data revealed close homology between the gene expression profiles of the ilium and femur. The gene expressions of Wnt-1, P75, SOX10, Nestin and Musashi-1 were significantly higher in the maxilla and mandible than in the ilium and femur. The frontal bone healed faster than the parietal bone. Parietal bone defects transplanted with maxillary and mandibular bone grafts exhibited closure. Thus, it is suggested that the maxilla and mandible have different gene expression profiles from the other bones examined, and exhibit neural crest cell properties with a marked healing ability in adults. The data further suggest that jaw bones are effective as both bone graft materials and graft beds.
2011-06-30 | GSE30167 | 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:The skull vault is composed of frontal and parietal bones that are connected by flexible sutures that protect the growing brain. Intramembranous ossification in the prenatal skull vault starts by mid-gestation in the mouse, and sutures must remain flexible for normal growth and development. Therefore, the balance of bone formation and remodeling needs to be precisely controlled because premature ossification in the sutures causes craniosynostosis (CS) to develop. CS has a variable clinical presentation where two frontal bones may be fused together, or a frontal bone may be fused to a parietal bone. While most studies focus on the premature suture ossification, we hypothesized that the process of intramembranous ossification in the frontal and parietal bones contributes to the etiology of CS. By bulk RNASeq we identified 536 unique transcripts between the frontal and parietal compartments.Taken together, we propose that the frontal bone is more active in bone remodeling than the parietal bone, and this control is important for temporal onset of intramembranous ossification in the skull vault.
2023-10-21 | GSE245664 | GEO
Project description:Previous investigations suggest that the different embryonic origins of the calvarial tissues (neural crest or mesoderm) may account for the different molecular mechanisms underlying sutural development. The aim of this study was to evaluate the differences in the gene expression of human cranial tissues and assess the presence of an expression signature reflecting their embryonic origins. Using microarray technology, we investigated global gene expression of cells from the frontal and parietal bones and the metopic and sagittal intrasutural mesenchyme (ISM) of four human fetal calvaria. Tissues samples were obtained from fetal crania of 4 normal human fetuses (two females ages 94 and 103 days and two males ages 97 and 98 days). All dural and extracranial soft tissues were removed from the parietal and frontal bones. 2-3 mm tissue compartments were excised from frontal and parietal bones and metopic and sagittal ISM. To avoid contamination with osteoblasts, ISM tissue was dissected from the central portion of each suture. Similarly, bone was harvested at least 3mm from the margin of the suture to avoid contamination with ISM. Media was changed every 3-4 days. After reaching 75-80% confluence, the cells were trypsinized with TrypLEExpress (Life Technologies, Denmark) and passaged. During the fourth and final passage, 180,000 cells were plated in triplicate in 6-well plates and cultured for 5 days followed by RNA extraction.
2015-08-03 | E-GEOD-62816 | biostudies-arrayexpress
Project description:Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is crucial to accelerate bone formation. In this context, the use of extracellular matrix (ECM) as natural 3D-framework mimicking in vivo tissue architecture is of interest. The aim of this study was to generate a devitalized human osteogenic MSC-derived ECM and to investigate its impact on MSC osteogenic differentiation to improve MSC properties in bone regeneration. The devitalized ECM significantly enhanced MSC adhesion and proliferation. Osteogenic differentiation and mineralization of MSCs on the ECM was quicker than in standard conditions. The presence of ECM promoted in vivo bone formation by MSCs in a mouse model of ectopic-calcification. We analyzed the ECM composition by mass spectrometry, detecting 846 proteins. Of these, 473 proteins were shared with the human bone proteome we previously described, demonstrating high homology to an in vivo microenvironment. Bioinformatic analysis of the 846 proteins showed involvement in adhesion and osteogenic differentiation, confirming the ECM composition as key modulator of MSC behaviour. In addition to known ECM-components, proteomic analysis revealed novel ECM functions, which could improve culture conditions. In summary, this study provides a simplified method to obtain an in vitro MSC-derived ECM that enhances osteogenic differentiation, and could be applied as natural biomaterial to accelerate bone regeneration.
2022-02-24 | PXD006865 | Pride
Project description:Objective: Craniofacial bone defects caused by injuries and congenital diseases are a formidable challenge to clinicians. Research has shown promise in using bone marrow mesenchymal stem cells (BM-MSCs) from limb bones for craniofacial bone regeneration; yet little is known about the potential of BM-MSCs from craniofacial bones. This study compared BM-MSCs isolated from limb and craniofacial bones in pigs, a preclinical model closely resembling humans. Design: Bone marrow was aspirated from the tibia and mandible of four-month-old pigs (n=4), followed by BM-MSC isolation, culture-expansion and confirmation by flow cytometry. Proliferation rates were compared using population doubling times. Osteogenic differentiation was evaluated by quantifying alkaline phosphatase (ALP) activity. Total mRNA was extracted from freshly isolated BM-MSCs and analyzed to compare gene expressions of tibial and mandibular BM-MSCs using an Affymetrix GeneChip porcine genome array, followed by real-time RT-PCR evaluation of two neural crest markers. Results: BM-MSCs from both locations expressed MSC markers without expression of hematopoietic markers. Mandibular BM-MSCs proliferated significantly faster than tibial BM-MSCs. Without osteogenic inducers, mandibular BM-MSC alkaline phosphatase activities were 3.3-fold greater than those of tibial origin. Microarray analysis identified 383 differentially expressed genes in mandibular and tibial BM-MSCs, including higher expression of cranial neural crest-related genes nestin and BMP-4 in mandibular BM-MSCs, a trend also confirmed by real-time RT-PCR. Among differently expressed genes, only 47 showed greater than 1.5-fold differences in expression. Conclusions: These data indicate that despite many similarities in gene expression, mandibular BM-MSCs express of number of genes differently than tibial BM-MSCs and have a phenotypic profile that may make them advantageous for craniofacial bone regeneration. Bone marrow was aspirated from the mandibular symphyseal region and the tibia of 3 pigs. Mesenchymal stem cells were isolated from the bone marrow and cultured to 80% confluence. Cells were harvested for total RNA extraction and the RNA was analyzed by Affymetrix GeneChip porcine genome array.
2016-05-14 | E-GEOD-81430 | biostudies-arrayexpress
Project description:TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi. Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. Cranial neural crest and cranial mesoderm cells were isolated by flow sorting of GFP reporter-labelled cells collected from heads of E9.5 mouse embryos. Three replicates were independently isolated and hybridized to Illumina mouse WG v 2.0 chips
2016-08-23 | E-GEOD-80335 | biostudies-arrayexpress
Project description:In order to study FGFR3’s role in cranial vault development, we generated the first fgfr3 loss-of-function zebrafish (fgfr3lof1/lof1). The mutant fish exhibited major changes in the craniofacial skeleton, with a lack of sutures, abnormal frontal and parietal bones, and the presence of ectopic bones. In order to define cellular and molecular processes responsible for this phenotype, we performed single-cell RNA sequencing of cranial vault cells from fgfr3lof1/lof1 and fgfr3+/+ zebrafish. Our data allow us to define transcriptomic profile of each osteogenic subpopulation involved in cranial vault formation and we revealed a defect in osteoblast differentiation associated with changes in the extracellular matrix. These findings demonstrate that fgfr3 is a positive regulator of osteogenesis and we conclude that changes in the extracellular matrix within growing bone impair cell-cell communication, mineralization, and new osteoblast recruitment.
2020-05-18 | GSE144944 | GEO
Project description:TWIST1, a basic helix-loop-helix transcription factor is essential for the development of cranial mesoderm and cranial neural crest-derived craniofacial structures. Our previous work showed that, in the absence of TWIST1, some cells within the cranial mesoderm adopt an abnormal epithelial configuration. Here, we show by transcriptome analysis that loss of TWIST1 in the cranial mesoderm is accompanied by a reduction in the expression of genes that are associated with cell-extracellular matrix interactions and the acquisition of mesenchymal characteristics. By comparing the transcriptional profiles of cranial mesoderm-specific Twist1 loss-of-function mutant and control mouse embryos, we identified a set of genes that are both TWIST1-dependent and predominantly expressed in the mesoderm. By ChIP-seq in a cell line model of a TWIST1-dependent mesenchymal state, we identified, among the downstream genes, three direct transcriptional targets of TWIST1: Ddr2, Pcolce and Tgfbi. Our findings show that the mesenchymal properties of the cranial mesoderm is likely to be regulated by a network of TWIST1 targets genes that influence the extracellular matrix and cell-matrix interactions, and collectively they are required for the morphogenesis of the craniofacial structures. Chromatin extracts were subject to chromatin immunoprecipitation with anti TWIST1 monoclonal antibody (ChIP-seq). Input chromatin, not subject to ChIP was used as the negative control. Two independent replicate experiments were performed. Purified, immunoprecipitated DNA was sequenced at Australian Genome Research facility.
2016-08-23 | E-GEOD-80662 | biostudies-arrayexpress