Human pluripotent stem cells-derived inner ear organoids recapitulate otic development in vitro.

Doda, Daniela; Jimenez, Sara Alonso; Rehrauer, Hubert; Carreño, Jose F; Valsamides, Victoria; Di Santo, Stefano; Widmer, Hans Ruedi; Edge, Albert; Locher, Heiko; van der Valk, Wouter; Zhang, Jingyuan; Koehler, Karl R; Roccio, Marta (2023). Human pluripotent stem cells-derived inner ear organoids recapitulate otic development in vitro. Development, 150(19) The Company of Biologists 10.1242/dev.201865

Text dev201865.pdf - Accepted Version Restricted to registered users only until 11 August 2024. Available under License Publisher holds Copyright. Download (4MB) | Request a copy

Our molecular understanding of the early stages of human inner ear development has been limited by the difficulty in accessing fetal samples at early gestational stages. As an alternative, previous studies have shown that inner ear morphogenesis can be partially recapitulated using induced pluripotent stem cells (iPSCs) directed to differentiate into Inner Ear Organoids (IEOs). Once validated and benchmarked, these systems could represent unique tools to complement and refine our understanding of human otic differentiation and model developmental defects. Here, we provide the first direct comparisons of the early human embryonic otocyst and fetal sensory organs to human IEOs. We use multiplexed immunostaining, and single-cell RNA sequencing to characterize IEOs at three key developmental steps, providing a new and unique signature of in vitro derived otic -placode, -epithelium, -neuroblasts, and -sensory epithelia. In parallel, we evaluate the expression and localization of critical markers at these equivalent stages in human embryos. Together, our data indicate that the current state-of-the-art protocol enables the specification of bona fide otic tissue, supporting the further application of IEOs to inform inner ear biology and disease.

Interest & Impact

Downloads

0 since deposited on 04 Oct 2023
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item