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对小鼠前腭的单细胞测序揭示了间质的异质性。

Single cell sequencing of the mouse anterior palate reveals mesenchymal heterogeneity.

机构信息

Section of Developmental Biology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

出版信息

Dev Dyn. 2023 Jun;252(6):713-727. doi: 10.1002/dvdy.573. Epub 2023 Feb 23.

Abstract

BACKGROUND

Cleft palate is one of the most prevalent birth defects. Mice are useful for studying palate development because of their morphological and genetic similarities to humans. In mice, palate development occurs between embryonic days (E)11.5 to 15.5. Single cell transcriptional profiles of palate cell populations have been a valuable resource for the craniofacial research community, but we lack a single cell transcriptional profile for anterior palate at E13.5, at the transition from proliferation to shelf elevation.

RESULTS

A detailed single cell RNA sequencing analysis reveals heterogeneity in expression profiles of the cell populations of the E13.5 anterior palate. Hybridization chain reaction RNA fluorescent in situ hybridization (HCR RNA FISH) reveals epithelial populations segregate into layers. Mesenchymal populations spatially segregate into four domains. One of these mesenchymal populations expresses ligands and receptors distinct from the rest of the mesenchyme, suggesting that these cells have a unique function. RNA velocity analysis shows two terminal cell states that contribute to either the proximal or distal palatal regions emerge from a single progenitor pool.

CONCLUSION

This single cell resolution expression data and detailed analysis from E13.5 anterior palate provides a powerful resource for mechanistic insight into secondary palate morphogenesis for the craniofacial research community.

摘要

背景

腭裂是最常见的出生缺陷之一。由于与人类在形态和遗传上具有相似性,因此老鼠是研究腭裂发育的有用模型。在老鼠中,腭裂发育发生在胚胎第 11.5 天至 15.5 天之间。腭细胞群体的单细胞转录谱为颅面研究界提供了宝贵的资源,但我们缺乏 E13.5 时(增殖向支架抬高过渡)的前腭单细胞转录谱。

结果

详细的单细胞 RNA 测序分析揭示了 E13.5 前腭细胞群体表达谱的异质性。杂交链反应 RNA 荧光原位杂交 (HCR RNA FISH) 显示上皮群体分离成层。间充质群体在空间上分离成四个区域。其中一个间充质群体表达的配体和受体与其余间充质不同,表明这些细胞具有独特的功能。RNA 速度分析表明,从单个祖细胞池中出现两个终末细胞状态,分别有助于腭的近端或远端区域。

结论

E13.5 前腭的单细胞分辨率表达数据和详细分析为颅面研究界提供了对次级腭形态发生的机制见解的有力资源。

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