Abstract
The super elongation complex (SEC) has been reported to play a key role in the proliferation and differentiation of mouse embryonic stem cells. However, the expression pattern and function of the SEC in the inner ear has not been investigated. Here, we studied the inner ear expression pattern of three key SEC components, AFF1, AFF4, and ELL3, and found that these three proteins are all expressed in both cochlear hair cells (HCs)and supporting cells (SCs). We also cultured Lgr5+ inner ear progenitors in vitro for sphere-forming assays and differentiation assays in the presence of the SEC inhibitor flavopiridol. We found that flavopiridol treatment decreased the proliferation ability of Lgr5+ progenitors, while the differentiation ability of Lgr5+ progenitors was not affected. Our results suggest that the SEC might play important roles in regulating inner ear progenitors and thus regulating HC regeneration. Therefore, it will be very meaningful to further investigate the detailed roles of the SEC signaling pathway in the inner ear in vivo in order to develop effective treatments for sensorineural hearing loss.
Highlights
Hearing loss occurs mainly due to noise exposure, aging, ototoxic drugs, and genetic factors (Sun et al, 2017)
We first measured the expression of the three key super elongation complex (SEC) subunits AFF1, AFF4, and ELL3 by reverse transcription-polymerase chain reaction (RT-PCR) (Figure 1A) and Western blotting analysis (Figures 1B,C), and we found that AFF1, AFF4, and ELL3 were all highly expressed in the cochlea
We further studied the expression pattern from both the obverse and lateral sides of AFF1, AFF4, and ELL3 in the cochlea of P3 and P40 mice and found that AFF1, AFF4, and ELL3 were all expressed in the cochlear hair cells (HCs) and supporting cells (SCs) (Figures 2A–D)
Summary
Hearing loss occurs mainly due to noise exposure, aging, ototoxic drugs, and genetic factors (Sun et al, 2017). Deafness has become a major global health problem, and sensorineural hearing loss is the most common type of hearing impairment (Youm and Li, 2018). Due to the lack of effective drugs and a non-invasive method for targeted delivery of drugs to the inner ear, the treatment options for sensorineural hearing loss are. Cochlear hair cells (HCs) in adult mammals lose the ability to regenerate, hearing deficits caused by HC loss are permanent (Warchol et al, 1993; Ryan, 2003; Cox et al, 2014; Xu et al, 2017; Chen et al, 2019). Induction of HC regeneration after injury by stimulating quiescent inner ear progenitor cells has been a main focus of auditory research in recent years
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