Dataset Information

Rbm24 promotes outer hair cell survival through Insm1 repression while independently regulating hair bundle morphogenesis

ABSTRACT: The inactivation of Rbm24, an RNA-binding protein, leads to cell death and hair bundle defects in cochlear outer hair cells (OHCs). However, the underlying molecular mechanisms remain unclear. To address this, we have performed comprehensive transcriptomic profiling of purified wild type and Rbm24-/- OHCs at postnatal day 7 (P7). Loss of Rbm24 perturbs numerous genes associated with hair bundle morphogenesis and delays the overall OHC differentiation program. Insm1, a key transcription factor normally downregulated by P2, remains aberrantly and persistently expressed in Rbm24-/- OHCs. Overexpression of Insm1 alone induces OHC death, whereas simultaneous inactivation of Rbm24 and Insm1 largely rescues OHC survival but only partially restores hair bundle morphology. It demonstrates that Rbm24 promotes OHC survival independently of its role in regulating hair bundle morphogenesis. Collectively, our findings establish Rbm24 as a dual function regulator that ensures OHC survival by acting as a critical repressor of Insm1 expression, while independently orchestrating hair bundle assembly. These results highlight the central role of Rbm24 in coordinating OHC differentiation and structural maturation and provide insights into potential molecular targets for hair cell regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE300428 | GEO | 2026/03/28

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The mouse auditory organ cochlea contains two types of sound receptors: inner hair cells (IHCs) and outer hair cells (OHCs). Tbx2 is expressed in IHCs but repressed in OHCs, and neonatal OHCs that misexpress Tbx2 transdifferentiate into IHC-like cells. However, the extent of this switch from OHCs to IHC-like cells and the underlying molecular mechanism remain poorly understood. Furthermore, whether Tbx2 can transform fully mature adult OHCs into IHC-like cells is unknown. Here, our single-cell transcriptomic analysis revealed that in neonatal OHCs misexpressing Tbx2, 85.6% of IHC genes, including Slc17a8, are upregulated, but only 38.6% of OHC genes, including Ikzf2 and Slc26a5, are downregulated. This suggests that Tbx2 cannot fully reprogram neonatal OHCs into IHCs. Moreover, Tbx2 also failed to completely reprogram cochlear progenitors into IHCs. Lastly, restoring Ikzf2 expression alleviated the abnormalities detected in Tbx2+ OHCs, which supports the notion that Ikzf2 repression by Tbx2 contributes to the transdifferentiation of OHCs into IHC-like cells. Our study evaluates the effects of ectopic Tbx2 expression on OHC lineage development at distinct stages of either male or female mice and provides molecular insights into how Tbx2 disrupts the gene-expression profile of OHCs. This research also lays the groundwork for future studies on OHC regeneration.Significance Statement Elucidation of the molecular and genetic mechanisms governing the determination and stability of cochlear inner hair cells (IHCs) and outer hair cells (OHCs) should provide valuable insights into the regeneration of damaged IHCs and OHCs. Here, we conditionally overexpress Tbx2 in vivo in cochlear sensory progenitors, neonatal OHCs, or adult OHCs. Our results show that Tbx2 overexpression alone can partially destabilize the OHC fate but cannot fully convert OHCs into IHCs. Specifically, we demonstrate that Ikzf2 repression due to Tbx2 overexpression is one of the key pathways disrupting the OHC fate.

Dataset Information

Rbm24 promotes outer hair cell survival through Insm1 repression while independently regulating hair bundle morphogenesis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets