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Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone

ABSTRACT: We report on explant osteoblast cultures from human patients, demonstrating that there are at least three sub-types of non-syndromic craniosynostosis defined by similarity of gene expression profiles. Osteoblast growth in culture, 23 craniosynostosis skull samples (7 metopic; 8 coronal; 3 lambdoid; 5 sagittal) and 8 normal (4 cranial bones and 4 long bones)

ORGANISM(S): Homo sapiens

SUBMITTER: Monica Rojas-Peña

PROVIDER: E-GEOD-55282 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone.

Rojas-Peña Monica L ML Olivares-Navarrete Rene R Hyzy Sharon S Arafat Dalia D Schwartz Zvi Z Boyan Barbara D BD Williams Joseph J Gibson Greg G

Journal of genomics 20140801

Craniosynostosis, the premature fusion of one or more skull sutures, occurs in approximately 1 in 2500 infants, with the majority of cases non-syndromic and of unknown etiology. Two common reasons proposed for premature suture fusion are abnormal compression forces on the skull and rare genetic abnormalities. Our goal was to evaluate whether different sub-classes of disease can be identified based on total gene expression profiles. RNA-Seq data were obtained from 31 human osteoblast cultures der ...[more]

PMID: 25184005

Similar Datasets

Characterization of distinct classes of differential gene expression in osteoblast cultures from non-syndromic craniosynostosis bone

Project description:We report on explant osteoblast cultures from human patients, demonstrating that there are at least three sub-types of non-syndromic craniosynostosis defined by similarity of gene expression profiles.

2014-07-16 | GSE55282 | GEO

The developing mouse coronal suture at single-cell resolution

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

BMP-dependent cellular dynamics during cranial suture establishment in zebrafish

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

Transcription profiling of protective bones of the skull (parietals) and weight-bearing bones of the limb (ulnae) in rats to obtain basal gene expression levels

Project description:Analysis of basal gene expression of the protective bones of the skull (parietals) and weight-bearing bones of the limb (ulnae) Experiment Overall Design: RNA extraction from normal bone

2008-11-22 | E-GEOD-12966 | biostudies-arrayexpress

The prenatal frontal and parietal bones are distinct organs.

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

Transcription profiling of mouse protective bones of the skull (parietals), weight-bearing bones of the limb (ulnae), mandibular bone and teeth to obtain basal gene expression levels

Project description:Pilot study; Analysis of basal gene expression of the protective bones of the skull (parietals), weight-bearing bones of the limb (ulnae) and mandibular bone and teeth Experiment Overall Design: RNA extraction from normal bone

2008-11-22 | E-GEOD-13563 | biostudies-arrayexpress

Comparative tissue gene expression profiling and alternative splicing by exon-sensitive microarrays in non-syndromic craniosynostosis

Project description:Craniosynostosis (CS) is the congenital premature fusion of one or more cranial sutures and represents the more prevalent craniofacial malformation in humans, with an overall incidence of 1 out of 2000-3000 live births. Non-syndromic craniosynostoses (NSC) are believed to be multifactorial disorders, with a strong genetic component, due to possible gene–gene or gene–environment interactions that remain to be clearly identified. In this study we delved into the molecular signaling acting in calvarial tissue and cells from patients affected by nonsynodromic midline craniosynostosis, using a comparative analysis between fused and unfused sutures of each affected individuals. Using comparative microarray tissue gene expression profiling we have identified a subset of genes involved in the structure and function of the primary cilium, including the Bardet-Biedl syndrome 9 (BBS9) gene, which was recently associated to sagittal synostosis in a GWAS study. We therefore characterized BBS9 expression and cilium-related signaling in cells isolated from patients’ calvarial bone.

2018-05-31 | GSE79386 | GEO

Basal gene expression in bone

Project description:Analysis of basal gene expression of the protective bones of the skull (parietals) and weight-bearing bones of the limb (ulnae)

2008-11-15 | GSE12966 | GEO

Pilot study: Basal gene expression in bone

Project description:Pilot study Analysis of basal gene expression of the protective bones of the skull (parietals), weight-bearing bones of the limb (ulnae) and mandibular bone and teeth

2008-11-15 | GSE13563 | GEO

Identification of differentially expressed proteins between fused and open sutures in sagittal nonsyndromic craniosynostosis during suture development by quantitative proteomic analysis

Project description:Craniosynostosis (CS) is a common birth defect due to the premature fusion of one or more cranial sutures. It manifests with abnormal skull shape and is associated with significant morbidities such as increased intracranial pressure, vision problems, and learning disabilities. Nonsyndromic craniosynostosis (NCS) occurs without any other associated birth defects and/or developmental delays and accounts for approximately 75% of all cases. Synostosis of the sagittal suture is the most common NCS subtype, accounting for 45-58% of all cases. Currently, surgical treatment is the only option to reshape the skull and allow for proper cranial growth. This surgical treatment is extensive and performed during the first year of life. Only one other study has examined the proteomic profile of cranial suture tissue derived from NCS patients. In order to understand how different proteins play a role in premature suture fusion and to potentially identify proteins that can serve as diagnostic and prognostic biomarkers for NCS, we identified biologically relevant differentially expressed proteins in NCS-derived tissues representing different stages in suture development.

2020-03-20 | MSV000085130 | MassIVE

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