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Series GSE188259 Query DataSets for GSE188259
Status Public on Nov 05, 2023
Title In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated coexpression of Atoh1 and Tbx2
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cochlear inner hair cells (IHCs) are primary sound receptors, and thus in efforts to develop treatments for hearing impairment. IHC regeneration in vivo has been widely attempted, although not yet in the IHC-damaged cochlea. Moreover, the extent to which new IHCs resemble wild-type IHCs remains unclear, as does whether new IHCs can yield hearing improvement. Here, we developed an in vivo mouse model wherein wild-type IHCs were pre-damaged and nonsensory supporting cells were transformed into IHCs by ectopically expressing Atoh1 transiently and Tbx2 permanently. Notably, the new IHCs expressed the functional marker vGlut3 and presented similar transcriptomic and electrophysiological properties as wild-type IHCs. Furthermore, the formation efficiency and maturity of new IHCs were higher than those previously reported, although marked hearing improvement was not achieved, at least partly due to defective mechanoelectrical transduction (MET) in new IHCs. Thus, we successfully regenerated new IHCs resembling wild-type IHCs in multiple aspects in the damaged cochlea. Our findings suggest that the defective MET is a critical barrier preventing the restoration of hearing capacity and should thus facilitate future IHC regeneration studies.
Overall design We have generated a new genetic mouse model wherein the endogenous inner hair cells (IHCs) are damaged, and at the same time transient Atoh1 and permanent Tbx2 expression are specifically induced in the neonatal cochlear inner border cells/inner phalangeal cells (IBCs/IPhs). Briefly, the IBCs/IPhs are transformed into new IHCs expressing functional IHC marker vGlut3. Comprehensive assays including fate mapping analysis, immunostaining, transcriptomic analysis, ultrastructure morphological and electrophysiological analysis, support that those new IHCs are functional at the single cell level and that they are divergent from the IBCs/IPhs and most closely to the endogenous IHCs.
Contributor(s) Li X, Bi Z, Ren M, Gu Y, Zhu T, Zhang Y, Li J, Li C, Wang G, Song L, Liu Z
Citation(s) 38078650
Submission date Nov 05, 2021
Last update date Dec 21, 2023
Contact name Minhui Ren
Phone 0086-21-54921793
Organization name Institution of Neuroscience, CAS
Street address 320 Yueyang Road
City Shanghai
ZIP/Postal code 200031
Country China
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM5673434 P42_IBCs_IPhs_10x
GSM5673435 P42_new_IHCs_10x
BioProject PRJNA778088
SRA SRP344722

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Supplementary file Size Download File type/resource
GSE188259_RAW.tar 102.1 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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