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Gli3 is a negative regulator of Tas1r3-expressing taste cells

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...

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Autores principales: Qin, Yumei, Sukumaran, Sunil K., Jyotaki, Masafumi, Redding, Kevin, Jiang, Peihua, Margolskee, Robert F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819828/
https://www.ncbi.nlm.nih.gov/pubmed/29415007
http://dx.doi.org/10.1371/journal.pgen.1007058
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author Qin, Yumei
Sukumaran, Sunil K.
Jyotaki, Masafumi
Redding, Kevin
Jiang, Peihua
Margolskee, Robert F.
author_facet Qin, Yumei
Sukumaran, Sunil K.
Jyotaki, Masafumi
Redding, Kevin
Jiang, Peihua
Margolskee, Robert F.
author_sort Qin, Yumei
collection PubMed
description 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 (Gli3(CKO)) had larger taste buds containing more taste cells than did control wild-type (Gli3(WT)) mice. In comparison to wild-type mice, Gli3(CKO) mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3(CKO) taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3(CKO) mice and/or organoids. Mirroring these changes, Gli3(CKO) 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.
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spelling pubmed-58198282018-03-15 Gli3 is a negative regulator of Tas1r3-expressing taste cells Qin, Yumei Sukumaran, Sunil K. Jyotaki, Masafumi Redding, Kevin Jiang, Peihua Margolskee, Robert F. PLoS Genet Research Article 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 (Gli3(CKO)) had larger taste buds containing more taste cells than did control wild-type (Gli3(WT)) mice. In comparison to wild-type mice, Gli3(CKO) mice had more Lgr5+ and Tas1r3+ cells, but fewer type III cells. Similar changes were observed ex vivo in Gli3(CKO) taste organoids cultured from Lgr5+ taste stem cells. Further, the expression of several taste marker and Gli3 target genes was altered in Gli3(CKO) mice and/or organoids. Mirroring these changes, Gli3(CKO) 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. Public Library of Science 2018-02-07 /pmc/articles/PMC5819828/ /pubmed/29415007 http://dx.doi.org/10.1371/journal.pgen.1007058 Text en © 2018 Qin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Qin, Yumei
Sukumaran, Sunil K.
Jyotaki, Masafumi
Redding, Kevin
Jiang, Peihua
Margolskee, Robert F.
Gli3 is a negative regulator of Tas1r3-expressing taste cells
title Gli3 is a negative regulator of Tas1r3-expressing taste cells
title_full Gli3 is a negative regulator of Tas1r3-expressing taste cells
title_fullStr Gli3 is a negative regulator of Tas1r3-expressing taste cells
title_full_unstemmed Gli3 is a negative regulator of Tas1r3-expressing taste cells
title_short Gli3 is a negative regulator of Tas1r3-expressing taste cells
title_sort gli3 is a negative regulator of tas1r3-expressing taste cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819828/
https://www.ncbi.nlm.nih.gov/pubmed/29415007
http://dx.doi.org/10.1371/journal.pgen.1007058
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