Single Cell Transcriptomics Reveal Abnormalities in Neurosensory Patterning of the Chd7 Mutant Mouse Ear

Area of Science:

• Developmental Biology
• Genetics
• Otolaryngology

Background:

• The chromatin remodeling protein CHD7 is essential for mammalian inner ear formation.
• Pathogenic variants in CHD7 cause CHARGE syndrome, leading to hearing loss and inner ear abnormalities.
• Reduced Chd7 dosage in the ear disrupts gene expression related to morphogenesis and neurogenesis, but its role in otic patterning is unclear.

Purpose of the Study:

• To define the roles of CHD7 in global gene expression regulation and patterning within the developing mouse ear.
• To investigate how Chd7 loss affects cell fate decisions and transcriptional identity in the otic system.

Main Methods:

• Single-cell multiplex qRT-PCR was employed to analyze the expression of 192 genes.
• FAC sorted cells from wild type and Chd7 mutant (Chd7Gt/+) microdissected mouse otocysts were analyzed.
• Gene expression patterns were compared between wild type and Chd7 haploinsufficient otocysts.

Main Results:

• Chd7 haploinsufficient otocysts showed a relative enrichment of neuroblast transcriptional identity compared to otic identity.
• Disruptions in pro-sensory and pro-neurogenic gene expression were observed in Chd7 loss-of-function models.
• Genes involved in Notch signaling pathways were among those showing altered expression.

Conclusions:

• CHD7 is required for early cell fate decisions during inner ear development.
• CHD7 plays a critical role in specific aspects of otic patterning and differentiation.
• Understanding CHD7's function provides insights into inner ear development and related congenital disorders.