Tmprss3欠損における内耳オルガノイド：蝸牛神経節ニューロンの特徴を研究するためのモデル

Organoids are valuable models to study human diseases. Cochlear implants (CIs) electrically stimulate spiral ganglion neurons (SGNs) to enable severely hearing-impaired people vocal communication. However, some studies found in patients with mutations in the TMPRSS3 gene that speech comprehension with CI was lower than for other etiologies. The reduced CI performance might be associated with reduced SGN excitability, the causes for which are largely unclear. We refined a protocol for generating SGN-like cells in otic organoids from human induced pluripotent stem cells (iPSC) and confirmed their identity through marker expression and electrophysiological characterization. TMPRSS3-deficient iPSC clones developed smaller and less differentiated organoids. Moreover, TMPRSS3-deficient SGN-like cells displayed smaller currents and were less likely to exhibit action potentials, which recapitulate the expected disease phenotype. Ultimately, we seek to use this organoid model to study SGN function in human patients for enhancing our understanding and prediction of CI performance.