The overexpression of Rps14 in Lgr5+ progenitor cells promotes hair cell regeneration in the postnatal mouse cochlea

被引：0

作者：

Ai J. ^{[1
]}

Jiang P. ^{[1
]}

Huang J. ^{[1
]}

Xiao H. ^{[1
]}

Lin Y. ^{[1
]}

Dai M. ^{[1
]}

Wang Y. ^{[1
]}

Zhang Y. ^{[2
,3
]}

Tian M. ^{[1
]}

Chai R. ^{[1
,4
,5
,6
,7
]}

Zhang S. ^{[1
]}

机构：

[1] State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Med

[2] Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing

[3] Research Institute of Otolaryngology, Nanjing

[4] Co-Innovation Center of Neuroregeneration, Nantong University, Nantong

[5] Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu

[6] Institute for Stem Cell and Regeneration, Chinese Academy of Science, Beijing

[7] Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing

来源：

Engineered Regeneration | 2023年 / 4卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Ectopic hair cells; Lgr5+ progenitor cells; Proliferation; Regeneration; Rps14; Trans-differentiation;

D O I：

10.1016/j.engreg.2023.04.006

中图分类号：

学科分类号：

摘要：

Sensory hair cells (HCs) in the cochlea cannot regenerate spontaneously in adult mammals after being damaged by external or genetic factors. However, several genes and signaling pathways are reported to induce cochlear HC regeneration at the early neonatal stage. Rps14 encodes a ribosomal protein that is involved in the regulation of cell differentiation and proliferation in mammals. However, its roles in the cochlea have not been reported in vivo. Here, we specifically overexpressed Rps14 in Lgr5+ progenitor cells in the newborn mouse cochlea and found that Rps14 conditional overexpression (cOE) mice had significantly increased the ectopic HCs, including inner and outer HCs. We further explored the source of these ectopic HCs and found no EdU+ supporting cells observed in the Rps14 cOE mice. The lineage tracing results, on the other hand, revealed that Rps14 cOE mice had significantly more tdTomato+ HCs in their cochleae than control mice. These results indicated that regenerated HCs by cOE of Rps14 are most likely derived from inducing the direct trans-differentiation of Lgr5+ progenitor cells into HCs. Moreover, real-time qPCR results suggested that the transcription factor genes Atoh1 and Gfi1, which are important in regulating HC differentiation, were upregulated in the cochlear basilar membrane of Rps14 cOE mice. In summary, this study provides in vivo evidence that, in the postnatal mouse cochlea, Rps14 is a potential gene that can promote the spontaneous trans-differentiation of Lgr5+ progenitor cells into HCs. This gene may one day be exploited as a therapeutic target for treating hearing loss. © 2023

引用

页码：328 / 336

页数：8

共 49 条

[1] Tao Y., Et al., AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration, Signal Transduct. Target. Ther., 7, (2022)
[2] Liu S., Wang S., Zou L., Xiong W., Mechanisms in cochlear hair cell mechano-electrical transduction for acquisition of sound frequency and intensity, Cell. Mol. Life Sci., 78, pp. 5083-5094, (2021)
[3] Brown C.S., Emmett S.D., Robler S.K., Tucci D.L., Global hearing loss prevention, Otolaryngol. Clin. N. Am., 51, pp. 575-592, (2018)
[4] Ding Y., Meng W., Kong W., He Z., Chai R., The role of FoxG1 in the inner ear, Front. Cell Dev. Biol., 8, (2020)
[5] Wagner E.L., Shin J.B., Mechanisms of hair cell damage and repair, Trends Neurosci., 42, pp. 414-424, (2019)
[6] Bermingham-McDonogh O., Reh T.A., Regulated reprogramming in the regeneration of sensory receptor cells, Neuron, 71, pp. 389-405, (2011)
[7] Warchol M.E., Lambert P.R., Goldstein B.J., Forge A., Corwin J.T., Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans, Science, 259, pp. 1619-1622, (1993)
[8] Chai R., Et al., Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea, J. Assoc. Res. Otolaryngol., 12, pp. 455-469, (2011)
[9] Zhang S., Et al., Frizzled-9+ supporting cells are progenitors for the generation of hair cells in the postnatal mouse cochlea, Front. Mol. Neurosci., 12, (2019)
[10] Bramhall N.F., Shi F., Arnold K., Hochedlinger K., Edge A.S., Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea, Stem Cell Rep., 2, pp. 311-322, (2014)

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