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Lgr5 阳性支持细胞在后生耳蜗中产生新的毛细胞。

Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea.

机构信息

Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA ; Program in Speech and Hearing Bioscience and Technology, Division of Health Sciences and Technology, Harvard and MIT, Cambridge, MA 02139, USA.

Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.

出版信息

Stem Cell Reports. 2014 Feb 20;2(3):311-22. doi: 10.1016/j.stemcr.2014.01.008. eCollection 2014 Mar 11.

Abstract

The prevalence of hearing loss after damage to the mammalian cochlea has been thought to be due to a lack of spontaneous regeneration of hair cells, the primary receptor cells for sound. Here, we show that supporting cells, which surround hair cells in the normal cochlear epithelium, differentiate into new hair cells in the neonatal mouse following ototoxic damage. Using lineage tracing, we show that new hair cells, predominantly outer hair cells, arise from Lgr5-expressing inner pillar and third Deiters cells and that new hair cell generation is increased by pharmacological inhibition of Notch. These data suggest that the neonatal mammalian cochlea has some capacity for hair cell regeneration following damage alone and that Lgr5-positive cells act as hair cell progenitors in the cochlea.

摘要

哺乳动物耳蜗损伤后听力损失的发生率被认为是由于毛细胞(声音的主要受体细胞)缺乏自发再生。在这里,我们表明,在正常耳蜗上皮中围绕毛细胞的支持细胞在新生小鼠的耳毒性损伤后会分化为新的毛细胞。通过谱系追踪,我们表明,新的毛细胞(主要是外毛细胞)来自 Lgr5 表达的内柱和第三 Deiters 细胞,并且 Notch 的药理学抑制可增加新毛细胞的产生。这些数据表明,新生哺乳动物耳蜗在单独损伤后具有一定的毛细胞再生能力,并且 Lgr5 阳性细胞在耳蜗中作为毛细胞祖细胞发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a53/3964281/1ee841cc2f58/fx1.jpg

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