Frontiers in Molecular Neuroscience (Oct 2021)

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

  • Natalia Smith-Cortinez,
  • Natalia Smith-Cortinez,
  • Rana Yadak,
  • Rana Yadak,
  • Ferry G. J. Hendriksen,
  • Eefje Sanders,
  • Dyan Ramekers,
  • Dyan Ramekers,
  • Robert J. Stokroos,
  • Robert J. Stokroos,
  • Huib Versnel,
  • Huib Versnel,
  • Louise V. Straatman,
  • Louise V. Straatman

DOI
https://doi.org/10.3389/fnmol.2021.729625
Journal volume & issue
Vol. 14

Abstract

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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.

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