Single cell RNA-seq in cholesteatoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18312
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Osaka University
• Principal Investigator: Shimizu Kotaro 大阪大学, 医学部附属病院, 医員 (60846492)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 中耳真珠腫 / 一細胞RNA解析 / 線維芽細胞

Outline of Final Research Achievements

We performed single cell RNA-seq in human cholesteatoma and identified a subset of cholesteatoma-specific fibroblasts that highly expressing inhibin βA (INHBA). Next, we confirmed that activin A, a dimer of INHBA, promotes osteoclast differentiation in vitro, and the deletion of INHBA in fibroblasts reduced osteoclast differentiation in mouse cholesteatoma model. These findings suggest that activin A-producing fibroblasts cause bone destruction by inducing local osteoclast differentiation and may be a potential therapeutic target.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

中耳真珠腫は近接する側頭骨やその内部構造物を溶解しながら進展し難聴、顔面神経麻痺、外側半規管瘻孔に伴うめまい、髄膜炎を発症しうる炎症性の疾患だが、骨破壊の機序は明らかになっていない。唯一の治療は外科的な切除だが、未だに有効な保存的治療手段はない。今回、我々は真珠腫の病原性線維芽細胞によって局所的な破骨細胞分化が誘導されることを明らかにし、線維芽細胞が保存的治療のターゲットになり得ることを示した。