| First Author | Holmes G | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 1 | Pages | 107871 |
| PubMed ID | 32640236 | Mgi Jnum | J:296375 |
| Mgi Id | MGI:6459225 | Doi | 10.1016/j.celrep.2020.107871 |
| Citation | Holmes G, et al. (2020) Integrated Transcriptome and Network Analysis Reveals Spatiotemporal Dynamics of Calvarial Suturogenesis. Cell Rep 32(1):107871 |
| abstractText | Craniofacial abnormalities often involve sutures, the growth centers of the skull. To characterize the organization and processes governing their development, we profile the murine frontal suture, a model for sutural growth and fusion, at the tissue- and single-cell level on embryonic days (E)16.5 and E18.5. For the wild-type suture, bulk RNA sequencing (RNA-seq) analysis identifies mesenchyme-, osteogenic front-, and stage-enriched genes and biological processes, as well as alternative splicing events modifying the extracellular matrix. Single-cell RNA-seq analysis distinguishes multiple subpopulations, of which five define a mesenchyme-osteoblast differentiation trajectory and show variation along the anteroposterior axis. Similar analyses of in vivo mouse models of impaired frontal suturogenesis in Saethre-Chotzen and Apert syndromes, Twist1(+/-) and Fgfr2(+/S252W), demonstrate distinct transcriptional changes involving angiogenesis and ribogenesis, respectively. Co-expression network analysis reveals gene expression modules from which we validate key driver genes regulating osteoblast differentiation. Our study provides a global approach to gain insights into suturogenesis. |
