TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae

Hair cell (HC) regeneration is a promising therapy for permanent sensorineural hearing loss caused by HC loss in mammals. Atoh1 has been shown to convert supporting cells (SCs) to HCs in neonatal cochleae; its combinations with other factors can improve the efficiency of HC regeneration. To identify...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhenhang Xu, Vikrant Rai, Jian Zuo
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hearing loss hair cell regeneration transcription factors atoh1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/683cc6893b2041a8857f91f34118b4a6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:683cc6893b2041a8857f91f34118b4a6
record_format	dspace
spelling	oai:doaj.org-article:683cc6893b2041a8857f91f34118b4a62021-11-08T05:27:15ZTUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae1662-510210.3389/fncel.2021.759223https://doaj.org/article/683cc6893b2041a8857f91f34118b4a62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.759223/fullhttps://doaj.org/toc/1662-5102Hair cell (HC) regeneration is a promising therapy for permanent sensorineural hearing loss caused by HC loss in mammals. Atoh1 has been shown to convert supporting cells (SCs) to HCs in neonatal cochleae; its combinations with other factors can improve the efficiency of HC regeneration. To identify additional transcription factors for efficient Atoh1-mediated HC regeneration, here we optimized the electroporation procedure for explant culture of neonatal mouse organs of Corti and tested multiple transcription factors, Six2, Ikzf2, Lbh, Arid3b, Hmg20 a, Tub, Sall1, and Znf532, for their potential to promote Atoh1-mediated conversion of SCs to HCs. These transcription factors are expressed highly in HCs but differentially compared to the converted HCs based on previous studies, and are also potential co-reprograming factors for Atoh1-mediated SC-to-HC conversion by literature review. P0.5 cochlear explants were electroporated with these transcription factors alone or jointly with Atoh1. We found that Sox2+ progenitors concentrated within the lateral greater epithelial ridge (GER) can be electroporated efficiently with minimal HC damage. Atoh1 ectopic expression promoted HC regeneration in Sox2+ lateral GER cells. Transcription factors Tub and Znf532, but not the other six tested, promoted the HC regeneration mediated by Atoh1, consistent with previous studies that Isl1 promotes Atoh1-mediated HC conversionex vivo and in vivo and that both Tub and Znf532 are downstream targets of Isl1. Thus, our studies revealed an optimized electroporation method that can transfect the Sox2+ lateral GER cells efficiently with minimal damage to the endogenous HCs. Our results also demonstrate the importance of the Isl1/Tub/Znf532 pathway in promoting Atoh1-mediated HC regeneration.Zhenhang XuZhenhang XuVikrant RaiJian ZuoFrontiers Media S.A.articlehearing losshair cellregenerationtranscription factorsatoh1Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hearing loss hair cell regeneration transcription factors atoh1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	hearing loss hair cell regeneration transcription factors atoh1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Zhenhang Xu Zhenhang Xu Vikrant Rai Jian Zuo TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
description	Hair cell (HC) regeneration is a promising therapy for permanent sensorineural hearing loss caused by HC loss in mammals. Atoh1 has been shown to convert supporting cells (SCs) to HCs in neonatal cochleae; its combinations with other factors can improve the efficiency of HC regeneration. To identify additional transcription factors for efficient Atoh1-mediated HC regeneration, here we optimized the electroporation procedure for explant culture of neonatal mouse organs of Corti and tested multiple transcription factors, Six2, Ikzf2, Lbh, Arid3b, Hmg20 a, Tub, Sall1, and Znf532, for their potential to promote Atoh1-mediated conversion of SCs to HCs. These transcription factors are expressed highly in HCs but differentially compared to the converted HCs based on previous studies, and are also potential co-reprograming factors for Atoh1-mediated SC-to-HC conversion by literature review. P0.5 cochlear explants were electroporated with these transcription factors alone or jointly with Atoh1. We found that Sox2+ progenitors concentrated within the lateral greater epithelial ridge (GER) can be electroporated efficiently with minimal HC damage. Atoh1 ectopic expression promoted HC regeneration in Sox2+ lateral GER cells. Transcription factors Tub and Znf532, but not the other six tested, promoted the HC regeneration mediated by Atoh1, consistent with previous studies that Isl1 promotes Atoh1-mediated HC conversionex vivo and in vivo and that both Tub and Znf532 are downstream targets of Isl1. Thus, our studies revealed an optimized electroporation method that can transfect the Sox2+ lateral GER cells efficiently with minimal damage to the endogenous HCs. Our results also demonstrate the importance of the Isl1/Tub/Znf532 pathway in promoting Atoh1-mediated HC regeneration.
format	article
author	Zhenhang Xu Zhenhang Xu Vikrant Rai Jian Zuo
author_facet	Zhenhang Xu Zhenhang Xu Vikrant Rai Jian Zuo
author_sort	Zhenhang Xu
title	TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
title_short	TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
title_full	TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
title_fullStr	TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
title_full_unstemmed	TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
title_sort	tub and znf532 promote the atoh1-mediated hair cell regeneration in mouse cochleae
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/683cc6893b2041a8857f91f34118b4a6
work_keys_str_mv	AT zhenhangxu tubandznf532promotetheatoh1mediatedhaircellregenerationinmousecochleae AT zhenhangxu tubandznf532promotetheatoh1mediatedhaircellregenerationinmousecochleae AT vikrantrai tubandznf532promotetheatoh1mediatedhaircellregenerationinmousecochleae AT jianzuo tubandznf532promotetheatoh1mediatedhaircellregenerationinmousecochleae
_version_	1718442915602104320

TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae

Ejemplares similares