Gli3 is a negative regulator of Tas1r3-expressing taste cells.
Gli3 is a negative regulator of Tas1r3-expressing taste cells.
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DOI：
10.1371/journal.pgen.1007058
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发表时间：
2018-03
期刊：
影响因子：
4.5
通讯作者：
Margolskee RF
中科院分区：
文献类型：
--
作者：
Qin Y;Sukumaran SK;Jyotaki M;Redding K;Jiang P;Margolskee RF
小鼠味觉受体细胞存活3-24天，需要在整个成年期再生。在舌前部，由基底味觉细胞亚群释放的音刺猬（SHH）调节干细胞中的转录因子Gli 2和Gli 3以控制味觉细胞再生。使用单细胞RNA-Seq，我们发现Gli 3在舌后部的Tas 1 r3表达味觉受体细胞和Lgr 5+味觉干细胞中高度表达。通过PCR和免疫组化检测，我们发现Gli 3在所有味觉区的味蕾中都有表达。后舌缺乏Gli 3的条件性基因敲除小鼠（Gli 3CKO）的味蕾比对照野生型小鼠（Gli 3 WT）的味蕾更大，含有更多的味觉细胞。与野生型小鼠相比，Gli 3CKO小鼠具有更多的Lgr 5+和Tas 1 r3+细胞，但III型细胞较少。在从Lgr 5+味觉干细胞培养的Gli 3CKO味觉类器官中离体观察到类似的变化。此外，在Gli 3CKO小鼠和/或类器官中，几种味觉标志物和Gli 3靶基因的表达发生了改变。模仿这些变化，Gli 3CKO小鼠增加舔甜和鲜味刺激，减少舔苦和酸味刺激，增加舌咽味觉神经反应甜和苦的化合物。我们的研究结果表明，Gli 3是一个抑制干细胞增殖，影响成熟的味觉细胞，特别是Tas 1 r3+细胞的数量和功能，在成人后舌。我们的发现揭示了Shh通路在成人味觉细胞再生中的作用，并可能有助于制定治疗化疗和衰老引起的味觉扭曲的策略。成年人的味觉细胞再生对于维持整个生命中的外周味觉细胞是必不可少的。Shh信号通路是胚胎和成体阶段味蕾发育和再生的重要调节因子。我们发现转录因子Gli 3是Shh通路的重要效应子，在Tas 1 r3表达的甜/鲜味味觉受体细胞和Lgr 5表达的味觉干细胞中表达。Gli 3基因的条件性缺失导致Tas 1 r3表达味觉细胞和Lgr 5表达干细胞数量的增加，沿着对苦味和甜味剂的反应改变。我们的发现揭示了成人味觉细胞的再生，并可能导致与衰老和化疗相关的味觉障碍的新治疗方法。
Mouse taste receptor cells survive from 3–24 days, necessitating their regeneration throughout adulthood. In anterior tongue, sonic hedgehog (SHH), released by a subpopulation of basal taste cells, regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration. Using single-cell RNA-Seq we found that Gli3 is highly expressed in Tas1r3-expressing taste receptor cells and Lgr5+ taste stem cells in posterior tongue. By PCR and immunohistochemistry we found that Gli3 was expressed in taste buds in all taste fields. Conditional knockout mice lacking Gli3 in the posterior tongue (Gli3CKO) had larger taste buds containing more taste cells than did control wild-type (Gli3WT) mice. In comparison to wild-type mice, Gli3CKO mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3CKO taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3CKO mice and/or organoids. Mirroring these changes, Gli3CKO mice had increased lick responses to sweet and umami stimuli, decreased lick responses to bitter and sour taste stimuli, and increased glossopharyngeal taste nerve responses to sweet and bitter compounds. Our results indicate that Gli3 is a suppressor of stem cell proliferation that affects the number and function of mature taste cells, especially Tas1r3+ cells, in adult posterior tongue. Our findings shed light on the role of the Shh pathway in adult taste cell regeneration and may help devise strategies for treating taste distortions from chemotherapy and aging. Adult taste cell regeneration is essential for maintaining peripheral taste cells throughout life. The Shh pathway is an important regulator of taste bud development and regeneration in both embryonic and adult stages. We show that the transcription factor Gli3, an important effector of the Shh pathway, is expressed in Tas1r3-expressing sweet/umami taste receptor cells and Lgr5-expressing taste stem cells. Conditional deletion of the Gli3 gene led to increased numbers of Tas1r3-expressing taste cells and Lgr5-expressing stem cells along with altered responses to bitter and sweet tastants. Our findings shed light on adult taste cell regeneration and may lead to new treatments of taste disorders associated with aging and chemotherapy.
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影响因子：
5.2
作者：
Thirumangalathu S;Barlow LA
通讯作者：
Barlow LA
味觉的细胞生物学。
影响因子：
7.8
作者：
Chaudhari, Nirupa;Roper, Stephen D.
通讯作者：
Roper, Stephen D.
影响因子：
5.3
作者：
Feng, Pu;Chai, Jinghua;Wang, Hong
通讯作者：
Wang, Hong
DOI：
10.1073/pnas.1004602107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Lee, Eunice Y.;Ji, Hongkai;Scott, Matthew P.
通讯作者：
Scott, Matthew P.
影响因子：
30.8
作者：
HUI, CC;JOYNER, AL
通讯作者：
JOYNER, AL