Abstract
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.
Highlights
Hearing loss affects almost 500 million people worldwide, including 34 million children (World Health Organization, 2021), and it has been estimated that 900 million people could have disabling hearing loss by 2050 (Wilson et al, 2017; Chadha et al, 2018)
It has been described that a subset of supporting cells (SCs) from the mouse and human cochlea have stem cell characteristics, and possess the potential to differentiate into new hair cells (HCs) in vitro and in vivo (Warchol et al, 1993; Li et al, 2003; White et al, 2006; McLean et al, 2017; Shu et al, 2019)
Cochlear leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expression has not been thoroughly described for adult mice, which is important since the majority of hearing-disabled people are adults (Cunningham and Tucci, 2017), so studying the role of LGR5+ SCs in adulthood is clinically very relevant
Summary
Hearing loss affects almost 500 million people worldwide, including 34 million children (World Health Organization, 2021), and it has been estimated that 900 million people could have disabling hearing loss by 2050 (Wilson et al, 2017; Chadha et al, 2018). It has been described that a subset of SCs from the mouse and human cochlea have stem cell characteristics, and possess the potential to differentiate into new HCs in vitro and in vivo (Warchol et al, 1993; Li et al, 2003; White et al, 2006; McLean et al, 2017; Shu et al, 2019). The leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is a membrane receptor in the Wnt pathway, which has been described as a stem-cell marker in different organs including the cochlea. It is expressed in a subgroup of SCs which give rise
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