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
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Neurochirurgie |
UniBE Contributor: |
Di Santo, Stefano, Widmer, Hans Rudolf |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1477-9129 |
Publisher: |
The Company of Biologists |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
04 Oct 2023 15:26 |
Last Modified: |
12 Aug 2024 00:25 |
Publisher DOI: |
10.1242/dev.201865 |
PubMed ID: |
37791525 |
Uncontrolled Keywords: |
Human otic development Inner ear Inner ear organoids Sensory epithelia development iPSC in vitro differentiation |
BORIS DOI: |
10.48350/186897 |
URI: |
https://boris.unibe.ch/id/eprint/186897 |
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