A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands.
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DOI:
10.1016/j.celrep.2022.110663
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发表时间:
2022-04-12
期刊:
影响因子:
8.8
通讯作者:
Makarenkova, Helen P.
Makarenkova, Helen P.
中科院分区:
生物学1区
文献类型:
--
作者:
Mauduit, Olivier;Aure, Marit H.;Delcroix, Vanessa;Basova, Liana;Srivastava, Amrita;Umazume, Takeshi;Mays, Jacqueline W.;Bellusci, Saverio;Tucker, Abigail S.;Hajihosseini, Mohammad K.;Hoffman, Matthew P.;Makarenkova, Helen P.

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成纤维细胞生长因子10(FGF 10)是一种间充质衍生的生长因子,是小鼠和人类胚胎器官发育的关键调节因子。使用唾液腺(SG)的单细胞RNA测序(RNA-seq)图谱和他莫昔芬诱导的Fgf 10 CreERT 2:R26-tdTomato小鼠,我们发现FGF 10 pos细胞在出生后第5天(P5)之前完全是间充质细胞,但在P7之后,表达发生了转变,并且在P15之后仅观察到上皮FGF 10 pos细胞。对分选的间充质和上皮FGF 10 pos细胞的进一步RNA-seq分析显示,上皮FGF 10 pos群体表达古老的离子细胞特征叉头盒i1和2(Foxi 1,Foxi 2)、Achaete-scute同源物3(Ascl 3)和囊性纤维化跨膜传导调节因子(Cftr)的标志。我们建议,上皮细胞FGF 10 pos是专门的SG离子细胞位于导管和重要的唾液的离子修饰。此外,它们通过与FGFR 2bpos导管和肌上皮细胞的通讯维持FGF 10依赖性腺体稳态。Mauduit等人在唾液腺中鉴定出独特的表达FGF 10的离子细胞。在出生后发育过程中,FGF 10表达从成纤维细胞转移到上皮离子细胞。离子细胞在唾液腺内环境稳定中发挥双重作用;它们维持唾液中的特定离子组成,并充当小生境细胞,为其他上皮细胞提供生长因子支持。
Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hallmarks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells. Mauduit et al. identified unique FGF10-expressing ionocytes in salivary glands. FGF10 expression shifts from fibroblasts to epithelial ionocytes during postnatal development. Ionocytes play a dual role in salivary gland homeostasis; they maintain specific ion composition in saliva and act as niche cells, providing growth factor support for other epithelial cells.
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