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

Single-cell analysis identifies a key role for Hhip in murine coronal suture development.
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DOI:
10.1038/s41467-021-27402-5
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发表时间:
2021-12-08
影响因子:
16.6
通讯作者:
Jabs EW
Jabs EW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Holmes G;Gonzalez-Reiche AS;Saturne M;Motch Perrine SM;Zhou X;Borges AC;Shewale B;Richtsmeier JT;Zhang B;van Bakel H;Jabs EW

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颅面发育取决于颅骨之间缝合线的形成和维持。在缝合线中,生长发生在沿着每块骨头边缘的成骨前沿,并且缝合线间充质将相邻的骨头分开。在这里,我们对胚胎、野生型小鼠冠状缝进行单细胞 RNA 序列分析,以确定其群体结构。 E16.5 处的 7 个群体和 E18.5 处的 9 个群体包括缝线间充质、成骨细胞和相关群体。 Hhip(一种刺猬信号传导抑制剂)的表达标志着间充质群体与其他神经颅缝的群体不同。对新生儿 Hhip 表达群体的追踪表明,后代细胞持续存在于冠状缝中,并有助于颅骨生长。在 E18.5 的 Hhip−/− 冠状缝中,与野生型相比,成骨前沿紧密排列,并且缝间充质因刺猬信号传导增加而耗尽。总的来说,这些数据表明 Hhip 是正常冠状缝发育所必需的。颅面发育取决于颅骨之间缝合线的形成和维持。在这里,作者鉴定了刺猬抑制剂 Hhip 的丰富表达,特别是在小鼠冠状缝的间充质中,并显示 Hhip−/− 突变体中的缝线发育不全。
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. Craniofacial development depends on formation and maintenance of sutures between bones of the skull. Here the authors identify enriched expression of the hedgehog inhibitor Hhip, specifically in the mesenchyme of the murine coronal suture, and show sutural dysgenesis in Hhip−/− mutants.
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