TY - JOUR
T1 - LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea
AU - Smith-Cortinez, Natalia
AU - Yadak, Rana
AU - Hendriksen, Ferry G J
AU - Sanders, Eefje
AU - Ramekers, Dyan
AU - Stokroos, Robert J
AU - Versnel, Huib
AU - Straatman, Louise V
N1 - Funding Information:
This research was funded by the Heinsius-Houbolt Foundation, Netherlands.
Funding Information:
We thank Corlinda ten Brink from the Cell Microscopy Core, Department of Cell Biology, Center for Molecular Medicine, UMC Utrecht for support in the confocal microscopy. We thank Jacco van Rheenen from the Netherlands Cancer Institute for providing p100 transgenic mice.
Publisher Copyright:
© Copyright © 2021 Smith-Cortinez, Yadak, Hendriksen, Sanders, Ramekers, Stokroos, Versnel and Straatman.
PY - 2021/10/5
Y1 - 2021/10/5
N2 - 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.
AB - 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.
KW - LGR5+ supporting cells
KW - adult mammalian cochlea
KW - deafness
KW - inner ear regeneration
KW - ototoxicity
UR - http://www.scopus.com/inward/record.url?scp=85117303149&partnerID=8YFLogxK
U2 - 10.3389/fnmol.2021.729625
DO - 10.3389/fnmol.2021.729625
M3 - Article
C2 - 34675775
SN - 1662-5099
VL - 14
SP - 1
EP - 9
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 729625
ER -