Nkx2-2 expressing taste cells in endoderm-derived taste papillae are committed to the type III lineage
Nkx2-2 expressing taste cells in endoderm-derived taste papillae are committed to the type III lineage
复制标题
内胚层来源的味觉乳头中表达 Nkx2-2 的味觉细胞属于 III 型谱系
DOI：
10.1016/j.ydbio.2021.05.020
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发表时间：
2021
影响因子：
2.7
通讯作者：
Margolskee Robert F.
中科院分区：
文献类型：
--
作者：
Qin Yumei;Sukumaran Sunil K.;Margolskee Robert F.
在哺乳动物中，多种细胞信号通路和转录因子调节胚胎味觉系统的发育和成年阶段味觉细胞的周转。使用小鼠味觉细胞的单细胞RNA-Seq，我们发现含有同源框的转录因子Nkx 2 -2，Sonic Hedgehog途径的靶点，以及体内多种细胞类型发育和再生的关键调节因子，在III型味觉细胞中高度表达，但在II型或味觉干细胞中不表达。利用原位杂交和免疫染色，我们证实，Nkx 2 - 2是专门表达在III型味觉细胞的内胚层衍生的轮廓和叶状味觉乳头，而不是在外胚层衍生的菌状乳头。谱系追踪显示，Nkx 2 -2表达细胞分化为III型，而不是II型或I型细胞的轮廓和叶状乳头。新生Nkx 2 -2敲除小鼠不表达关键的III型味觉细胞标记基因，而II型和I型味觉细胞标记基因的表达在这些小鼠中不受影响。我们的研究结果表明，Nkx 2 -2表达细胞致力于III型谱系，Nkx 2 -2可能是关键的III型味觉细胞在舌后部的发展，从而说明了一个关键的差异，在机制的III型细胞谱系规范之间的外胚层和内胚层衍生的味觉领域。
In mammals, multiple cell-signaling pathways and transcription factors regulate development of the embryonic taste system and turnover of taste cells in the adult stage. Using single-cell RNA-Seq of mouse taste cells, we found that the homeobox-containing transcription factorNkx2-2,a target of the Sonic Hedgehog pathway and a key regulator of the development and regeneration of multiple cell types in the body, is highly expressed in type III taste cells but not in type II or taste stem cells. Usingin situhybridization and immunostaining, we confirmed thatNkx2-2is expressed specifically in type III taste cells in the endoderm-derived circumvallate and foliate taste papillae but not in the ectoderm-derived fungiform papillae. Lineage tracing revealed thatNkx2-2-expressing cells differentiate into type III, but not type II or type I cells in circumvallate and foliate papillae. NeonatalNkx2-2-knockout mice did not express key type III taste cell marker genes, while the expression of type II and type I taste cell marker genes were unaffected in these mice. Our findings indicate thatNkx2-2-expressing cells are committed to the type III lineage and thatNkx2-2 may be critical for the development of type III taste cells in the posterior tongue, thus illustrating a key difference in the mechanism of type III cell lineage specification between ectoderm- and endoderm-derived taste fields.