LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea

• Main Authors: Natalia Smith-Cortinez, Rana Yadak, Ferry G. J. Hendriksen, Eefje Sanders, Dyan Ramekers, Robert J. Stokroos, Huib Versnel, Louise V. Straatman
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-10-01
• Series: Frontiers in Molecular Neuroscience
• Subjects: inner ear regeneration; deafness; LGR5+ supporting cells; ototoxicity; adult mammalian cochlea
• Online Access: https://www.frontiersin.org/articles/10.3389/fnmol.2021.729625/full

Sensorineural hearing loss is mainly caused by irreversible damage to sensory hair cells (HCs). A subgroup of supporting cells (SCs) in the cochlea express leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a marker for tissue-resident stem cells. LGR5+ SCs could be used as an endogenous source of stem cells for regeneration of HCs to treat hearing loss. Here, we report long-term presence of LGR5+ SCs in the mature adult cochlea and survival of LGR5+ SCs after severe ototoxic trauma characterized by partial loss of inner HCs and complete loss of outer HCs. Surviving LGR5+ SCs (confirmed by GFP expression) were located in the third row of Deiters’ cells. We observed a change in the intracellular localization of GFP, from the nucleus in normal-hearing to cytoplasm and membrane in deafened mice. These data suggests that the adult mammalian cochlea possesses properties essential for regeneration even after severe ototoxic trauma.