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The developing mouse coronal suture at single-cell resolution

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE163693 | GEO | 2021/06/17

REPOSITORIES: GEO

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Single-cell analysis identifies a key role for Hhip in murine coronal suture development

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

Skeletal Stem Cell Powering Cranial Suture Fate: An Answer to Craniosynostosis (scRNA-seq)

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Skeletal Stem Cell Powering Cranial Suture Fate: An Answer to Craniosynostosis (bulk_RNA-seq)

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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.

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Calvarial osteoblast transcriptome analysis identifies genetic targets and extracellular matrix-mediated focal adhesion as potential biomarkers for single-suture craniosynostosis

Project description:Craniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of isolated single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive at best. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as potential genetic biomarkers for single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Furthermore, pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single-suture synostosis and controls. Lastly, overall gene expression was found to be highly conserved between coronal and metopic cases, as evidenced by the fact that WNT2 and IGFBP2 were the only differentially regulated genes identified in a direct comparison. These results not only confirm the roles of previously reported craniosynostosis-related targets but also introduce novel genetic biomarkers and pathways that may play critical roles in its pathogenesis. In this study, gene expression data from 199 patients with isolated sagittal (n= 100), unilateral coronal (n = 50), and metopic (n = 49) synostosis are compared against both a control population (n = 50), as well as each other.

2012-03-04 | E-GEOD-27976 | biostudies-arrayexpress

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2013-09-12 | E-GEOD-50796 | biostudies-arrayexpress

Modifiers and Mediators of Craniosynostosis Severity Revealed by Differential Gene Expression

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2014-07-16 | E-GEOD-55282 | biostudies-arrayexpress

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