AAV-mediated Gpm6b expression supports hair cell reprogramming

Qiuhan Sun; Liyan Zhang; Tian Chen; Nianci Li; Fangzhi Tan; Xingliang Gu; Yinyi Zhou; Ziyu Zhang; Yicheng Lu; Jie Lu; Xiaoyun Qian; Bing Guan; Jieyu Qi; Fanglei Ye; Renjie Chai

doi:10.1111/cpr.13620

AAV-mediated Gpm6b expression supports hair cell reprogramming

Qiuhan Sun, Liyan Zhang, Tian Chen, Nianci Li, Fangzhi Tan^*, Xingliang Gu, Yinyi Zhou, Ziyu Zhang, Yicheng Lu, Jie Lu, Xiaoyun Qian, Bing Guan^*, Jieyu Qi^*, Fanglei Ye^*, Renjie Chai^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5⁺ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

Original language	English
Article number	e13620
Journal	Cell Proliferation
Volume	57
Issue number	7
DOIs	https://doi.org/10.1111/cpr.13620
Publication status	Published - Jul 2024
Externally published	Yes

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title = "AAV-mediated Gpm6b expression supports hair cell reprogramming",

abstract = "Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.",

author = "Qiuhan Sun and Liyan Zhang and Tian Chen and Nianci Li and Fangzhi Tan and Xingliang Gu and Yinyi Zhou and Ziyu Zhang and Yicheng Lu and Jie Lu and Xiaoyun Qian and Bing Guan and Jieyu Qi and Fanglei Ye and Renjie Chai",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.",

year = "2024",

month = jul,

doi = "10.1111/cpr.13620",

language = "English",

volume = "57",

journal = "Cell Proliferation",

issn = "0960-7722",

publisher = "Wiley-Blackwell Publishing Ltd",

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TY - JOUR

T1 - AAV-mediated Gpm6b expression supports hair cell reprogramming

AU - Sun, Qiuhan

AU - Zhang, Liyan

AU - Chen, Tian

AU - Li, Nianci

AU - Tan, Fangzhi

AU - Gu, Xingliang

AU - Zhou, Yinyi

AU - Zhang, Ziyu

AU - Lu, Yicheng

AU - Lu, Jie

AU - Qian, Xiaoyun

AU - Guan, Bing

AU - Qi, Jieyu

AU - Ye, Fanglei

AU - Chai, Renjie

PY - 2024/7

Y1 - 2024/7

N2 - Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

AB - Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

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U2 - 10.1111/cpr.13620

DO - 10.1111/cpr.13620

M3 - Article

C2 - 38400824

AN - SCOPUS:85186443738

SN - 0960-7722

VL - 57

JO - Cell Proliferation

JF - Cell Proliferation

IS - 7

M1 - e13620

ER -

AAV-mediated Gpm6b expression supports hair cell reprogramming

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