ArticleRegenerative therapy2022
Critical roles of FGF, RA, and WNT signalling in the development of the human otic placode and subsequent lineages in a dish.
Article in Regenerative therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Jervell and Lange-Nielsen Syndrome Related Clinical Genetics and Experimental Models.Pediatric discovery · 2026Review
- The Whole Transcriptome Sequencing Profile of Serum-Derived Exosomes and Potential Pathophysiology of Age-Related Hearing Loss.Diagnostics (Basel, Switzerland) · 2026Article
- Review
- From Genes to Disease: ReassessingInternational journal of molecular sciences · 2025Article
- Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity.Cell death & disease · 2024Article
- Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells.Biomedicines · 2024Review
- Onco-Ontogeny of Squamous Cell Cancer of the First Pharyngeal Arch Derivatives.International journal of molecular sciences · 2024Review
- Tissue engineering strategies for spiral ganglion neuron protection and regeneration.Journal of nanobiotechnology · 2024Review
- Advance and Application of Single-cell Transcriptomics in Auditory Research.Neuroscience bulletin · 2024Review
- Induced Pluripotent Stem Cells, a Stepping Stone to In Vitro Human Models of Hearing Loss.Cells · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Efficient induction of the otic placode, the developmental origin of the inner ear from human pluripotent stem cells (hPSCs), provides a robust platform for otic development and sensorineural hearing loss modelling. Nevertheless, there remains a limited capacity of otic lineage specification from hPSCs by stepwise differentiation methods, since the critical factors for successful otic cell differentiation have not been thoroughly investigated. In this study, we developed a novel differentiation system involving the use of a three-dimensional (3D) floating culture with signalling factors for generating otic cell lineages via stepwise differentiation of hPSCs. Methods: We differentiated hPSCs into preplacodal cells under a two-dimensional (2D) monolayer culture. Then, we transferred the induced preplacodal cells into a 3D floating culture under the control of the fibroblast growth factor (FGF), bone morphogenetic protein (BMP), retinoic acid (RA) and WNT signalling pathways. We evaluated the characteristics of the induced cells using immunocytochemistry, quantitative PCR (qPCR), population averaging, and single-cell RNA-seq (RNA-seq) analysis. We further investigated the methods for differentiating otic progenitors towards hair cells by overexpression of defined transcription factors. Results: We demonstrated that hPSC-derived preplacodal cells acquired the potential to differentiate into posterior placodal cells in 3D floating culture with FGF2 and RA. Subsequent activation of WNT signalling induced otic placodal cell formation. By single-cell RNA-seq (scRNA-seq) analysis, we identified multiple clusters of otic placode- and otocyst marker-positive cells in the induced spheres. Moreover, the induced otic cells showed the potential to generate hair cell-like cells by overexpression of the transcription factors Conclusions: We demonstrated the critical role of FGF2, RA and WNT signalling in a 3D environment for the
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