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Journal of the Association for Research in Otolaryngology

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12-03-2024 | Original Article

A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2⁺ Progenitors in the Neonatal Mouse Inner Ear Organoids

Authors: Wenjin Wu, Penghui Chen, Jun Yang, Yupeng Liu

Published in: Journal of the Association for Research in Otolaryngology | Issue 2/2024

Abstract

Purpose

To investigate the impact of rapamycin on the differentiation of hair cells.

Methods

Murine cochlear organoids were derived from cochlear progenitor cells. Different concentrations of rapamycin were added into the culture medium at different proliferation and differentiation stages.

Results

Rapamycin exhibited a concentration-dependent reduction in the proliferation of these inner ear organoids. Nevertheless, organoids subjected to a 10-nM dose of rapamycin demonstrated a markedly increased proportion of hair cells. Furthermore, rapamycin significantly upregulated the expression of markers associated with both hair cells and supporting cells, including ATOH1, MYO7A, and SOX2. Mechanistic studies revealed that rapamycin preferentially suppressed cells without Sox2 expression during the initial proliferation stage, thereby augmenting and refining the population of SOX2⁺ progenitors. These enriched progenitors were predisposed to differentiate into hair cells during the later stages of organoid development. Conversely, the use of the mTOR activator MHY 1485 demonstrated opposing effects.

Conclusion

Our findings underscore a practical strategy for enhancing the generation of inner ear organoids with a low dose of rapamycin, achieved by enriching SOX2⁺ progenitors in an in vitro setting.

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Title: A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2+ Progenitors in the Neonatal Mouse Inner Ear Organoids
Authors: Wenjin Wu
Penghui Chen
Jun Yang
Yupeng Liu
Publication date: 12-03-2024
Publisher: Springer US
Published in: Journal of the Association for Research in Otolaryngology / Issue 2/2024
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI: https://doi.org/10.1007/s10162-024-00938-1

At a glance: The STEP trials

Springer Medicine

A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2⁺ Progenitors in the Neonatal Mouse Inner Ear Organoids

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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