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Thyroid hormone-induced expression of Foxl1 in subepithelial fibroblasts correlates with adult stem cell development during Xenopus intestinal remodeling
Scientific Reports ( IF 4.6 ) Pub Date : 2020-11-26 , DOI: 10.1038/s41598-020-77817-1
Takashi Hasebe , Kenta Fujimoto , Atsuko Ishizuya-Oka

In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one. We have previously shown that connective tissue cells surrounding the epithelium are essential for the stem cell development. To clarify whether such cells correspond to mammalian Foxl1-expressing mesenchymal cells, which have recently been shown to be a critical component of intestinal stem cell niche, we here examined the expression profile of Foxl1 in the X. laevis intestine by using RT-PCR and immunohistochemistry. Foxl1 expression was transiently upregulated only in connective tissue cells during the early period of metamorphic climax and was the highest just beneath the proliferating stem/progenitor cells. In addition, electron microscopic analysis showed that these subepithelial cells are ultrastructurally identified as telocytes like the mammalian Foxl1-expressing cells. Furthermore, we experimentally showed that Foxl1 expression is indirectly upregulated by thyroid hormone (TH) through Shh signaling and that TH organ-autonomously induces the Foxl1-expressing cells concomitantly with appearance of the stem cells in the tadpole intestine in vitro. The present results suggest that intestinal niche cells expressing Foxl1 are evolutionally conserved among terrestrial vertebrates and can be induced by TH/Shh signaling during amphibian metamorphosis for stem cell development.



中文翻译:

甲状腺激素诱导的上皮下成纤维细胞中Foxl1的表达与非洲爪蟾肠道重构过程中成年干细胞发育相关

非洲爪蟾(Xenopus laevis)肠变态期间,干细胞出现并产生类似于哺乳动物的成年上皮细胞。先前我们已经证明,上皮周围的结缔组织细胞对于干细胞发育至关重要。为了澄清此类细胞是否对应于哺乳动物的表达Foxl1的间充质细胞,最近已证明它们是肠道干细胞生态位的关键组成部分,我们在这里检查了X. laevis中Foxl1的表达谱通过RT-PCR和免疫组织化学检测肠道。在变质高潮的早期,Foxl1表达仅在结缔组织细胞中瞬时上调,并且在增殖的干/祖细胞下方最高。另外,电子显微镜分析表明,这些超上皮下细胞被超微结构鉴定为像哺乳动物的Fox11表达细胞那样的端粒细胞。此外,我们实验性地表明,Foxl1表达通过Shh信号被甲状腺激素(TH)间接上调,并且TH器官在体外与test细胞一起自主诱导表达Foxl1的细胞以及干细胞的出现。

更新日期:2020-11-27
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