ZBTB20 is essential for cochlear maturation and hearing in mice

Xie, Zhifang; Ma, Xianhua; Bai, Qiufang; Tang, Jie; Sun, Jian-he; Jiang, Fei; Guo, Weiwei; Wang, Chen-Ma; Yang, Rui; Wen, Yin-Chuan; Wang, Fangyuan; Chen, Yu-Xia; Zhang, Hai; He, David Z.Z.; Kelley, Matthew W.; Yang, Shiming; Zhang, Weiping J.

doi:10.1073/pnas.2220867120

Cited by 7 publications

(17 citation statements)

References 72 publications

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“…Our previous work, along with studies by others, has demonstrated that root cell cytoplasm and their processes exhibit enrichment of acetyl-α-tubulin (Jagger and Forge, 2013; Liu et al, 2018; Xie et al, 2023). To gain further insight into root cell morphology, we conducted immunofluorescence staining for acetyl-α-tubulin.…”

Section: Resultsmentioning

confidence: 67%

Targeted Deletion of All Known Thyroid Hormone Receptors Causes Maturation Retardation and Early-onset Degeneration of Cochlear Outer Sulcus

Ma,

Jiang,

Wei

et al. 2023

Preprint

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Thyroid hormone (TH) and/or its receptors (TRs) are essential for hearing, cochlear late-stage development and maintaining endocochlear potential (EP). The mechanism underlying the EP reduction upon deficiency of TH or TRs remains unknown. The cochlear outer sulcus (root cell) is considered to be important for the maintenance of endolymph homeostasis and EP, and undergoes dramatic morphological changes during cochlear late-stage developmental window. It has been long neglected whether TH and/or TRs are required for root cell differentiation and function. Here we demonstrate a key role for TH or TRs in postnatal root cell development and survival in mice. Anti-thyroid drug-induced developmental hypothyroidism results in severe retardation in root cell differentiation. Targeted deletion of both TRα and TRβ but not individual TRβ in cochlear epithelium causes a similar impairment, compounded with an early-onset degeneration of root cells and a reduced EP, without obvious alterations in stria vascularis. Furthermore, we demonstrate that TH signaling acts in parallel with ZBTB20 in the outer sulcus, a transcription factor which we have recently reported to be essential for the outer sulcus differentiation. Our results support that TRα and TRβ act redundantly in promoting root cell late-stage differentiation and maintaining its cellular homeostasis, and root cell dysfunction at least partially contribute to a reduced EP upon deficiency of TH or TRs. These findings imply that root cells may play an important role in maintaining the health of cochlear sensory epithelium and normal EP.Significance StatementThyroid hormone (TH) and/or its receptors (TRs) are essential for hearing and cochlear development. The cochlear outer sulcus (root cell) is considered to be important for cochlear ionic and metabolic homeostasis. We found that combined deletion of both TRα and TRβ but not individual TRβ results in severe retardation in root cell differentiation accompanied by an early-onset degeneration and a reduced endocochlear potential (EP), suggesting TRα and TRβ act redundantly in promoting root cell differentiation and maintaining its cellular homeostasis. Our findings suggest that root cell dysfunction may at least partially contribute to a reduced EP upon deficiency of TRs, and root cells may play an important role in maintaining the health of cochlear sensory epithelium and EP.

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Section: Resultsmentioning

confidence: 67%

Targeted Deletion of All Known Thyroid Hormone Receptors Causes Maturation Retardation and Early-onset Degeneration of Cochlear Outer Sulcus

Ma,

Jiang,

Wei

et al. 2023

Preprint

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“…Xie et al ( 4 ) conducted a study investigating the effect of ZBTB20 on cochlear development and hearing in mice. Their findings suggest that the ZBTB20 gene is crucial for the growth of the cochlear lateral non-sensory epithelium, hearing perception, and for overall cochlear development.…”

Section: Discussionmentioning

confidence: 99%

Cochlear Implantation in Primrose Syndrome with a Novel ZBTB20 Gene Variant

Tuğci,

Gezdirici,

Aşaroğlu

et al. 2023

TAO

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In this article, we aim to present details of the cochlear implantation procedure performed in a patient with Primrose syndrome, which is a rare genetic condition characterized by physical deformities, sensorineural hearing loss, and metabolic disorders. While its long-term prognosis is still under investigation, the absence of intraoperative and postoperative complications indicates promising findings. This designates cochlear implantation as a viable therapeutic approach for sensorineural hearing loss linked to Primrose syndrome. As cochlear implantation in cases with Primrose syndrome has not been discussed previously in the literature and our patient has recently been operated on, additional investigation is imperative to broaden the understanding of cochlear implant outcomes in this patient population.

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“…All the SC clusters expressed known pan-SC markers like GFAP, KREMEN1, OTOL1, and SOX2, while the SC-like cell expressed cluster-speci c genes like ANKRD1, KRT7 and CRYAB. Speci cally, SC-1 is characterized by OTOL1, SPARCL1, and ZBTB20, a TF required for cochlear terminal differentiation and hearing 23 . SC-2 is marked by KRT19, STMN1, APOE, CYR61, RBP1, and TFs ID1 and ID3.…”

Section: Transcriptional Heterogeneity Of the Adult Human Utricle Sen...mentioning

confidence: 99%

Revealing heterogeneity and damage response in the adult human utricle

Dabdoub,

Luca,

Ibeh

et al. 2024

Preprint

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The human utricle is a vestibular organ responsible for maintaining balance. Balance function commonly deteriorates with age. With the aging population expected to double to 2 billion by 2050 and no pharmaceutical or biological treatments currently available, balance disorders are a significant unmet medical need. The utricle is composed of sensory and non-sensory cells, which are closely related, and non-sensory cells have a limited capacity to regenerate sensory cells in a damaged balance organ and, therefore, are a relevant therapeutic target. Here, we show the cellular and transcriptional profiles of the adult human utricle and its response to damage by performing bulk and single-cell RNA-sequencing from patient-derived utricles. We discovered six transcriptionally distinct non-sensory cell types, including a novel population, demonstrating the heterogeneity of the adult human utricle. In addition, using an aminoglycoside damage paradigm, we determined the early transcriptional changes of the utricle after damage. Our findings demonstrate that this organ has the capacity to respond to ototoxic damage within 24 h and potentially initiate a regenerative response via an early-responding supporting cell population. This study represents a major step forward in inner ear regenerative medicine, and our results will serve as a foundation for preclinical studies, paving the way to therapeutic strategies for balance recovery.

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ZBTB20 is essential for cochlear maturation and hearing in mice

Cited by 7 publications

References 72 publications

Targeted Deletion of All Known Thyroid Hormone Receptors Causes Maturation Retardation and Early-onset Degeneration of Cochlear Outer Sulcus

Targeted Deletion of All Known Thyroid Hormone Receptors Causes Maturation Retardation and Early-onset Degeneration of Cochlear Outer Sulcus

Cochlear Implantation in Primrose Syndrome with a Novel ZBTB20 Gene Variant

Revealing heterogeneity and damage response in the adult human utricle

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