Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Nat Commun. 2021 Dec 8;12(1):7132. doi: 10.1038/s41467-021-27402-5.
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. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.
颅面发育依赖于颅骨骨骼之间的缝的形成和维持。在缝中，生长发生在沿着每个骨边缘的成骨前缘，而缝间质将相邻的骨骼分开。在这里，我们对胚胎期、野生型鼠冠状缝进行了单细胞 RNA-seq 分析，以确定其群体结构。E16.5 时有 7 个群体，E18.5 时有 9 个群体构成了缝间质、成骨细胞和相关群体。 hedgehog 信号抑制剂 Hhip 的表达标志着与其他神经颅缝不同的间充质群体。对新生 Hhip 表达群体的追踪表明，后代细胞在冠状缝中持续存在，并有助于颅骨骨生长。与野生型相比，在 E18.5 的 Hhip 冠状缝中，成骨前缘紧密贴合，缝间质耗竭， hedgehog 信号增加。总的来说，这些数据表明 Hhip 是正常冠状缝发育所必需的。
