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Human pluripotent stem cell-derived inner ear organoids recapitulate otic development in vitro
Daniela Doda1,2, Sara Alonso Jimenez1,2, Hubert Rehrauer2,3
1Inner Ear Stem Cell Laboratory, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich (USZ), 8091 Zurich,Switzerland.
Development (Cambridge, England)
|October 4, 2023
Summary
Human inner ear organoids (IEOs) offer a new way to study early development. This research compares IEOs to human embryos, validating IEOs for understanding inner ear biology and disease.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Otic Development
Background:
- Studying early human inner ear development is challenging due to limited access to embryonic samples.
- Induced pluripotent stem cells (iPSCs) can be differentiated into inner ear organoids (IEOs) to model development.
- Validated IEOs can serve as valuable tools for understanding otic differentiation and developmental defects.
Purpose of the Study:
- To directly compare human IEOs with early human embryonic otocysts and fetal sensory organs.
- To characterize the molecular signature of in vitro-derived otic tissues at key developmental stages.
- To validate the utility of IEOs for studying human inner ear development and disease.
Main Methods:
- Multiplexed immunostaining of IEOs and human embryonic/fetal tissues.
- Single-cell RNA-sequencing (scRNA-seq) to profile IEOs.
- Comparative analysis of gene expression and protein localization markers.
Main Results:
- IEOs at three developmental stages were characterized, revealing unique molecular signatures for otic placode, epithelium, neuroblasts, and sensory epithelia.
- Crucial marker expression and localization in IEOs were evaluated and compared to equivalent stages in human embryos.
- Data indicate that the current protocol successfully specifies bona fide otic tissue in IEOs.
Conclusions:
- Human IEOs accurately recapitulate key aspects of early inner ear development.
- The validated IEO model provides a powerful platform for investigating inner ear biology.
- IEOs hold significant potential for modeling inner ear developmental defects and informing disease research.
Related Concept Videos
01:22Hair Cells
Hair cells are the sensory receptors of the auditory system—they transduce mechanical sound waves into electrical energy that the nervous system can understand. Hair cells are located in the organ of Corti within the cochlea of the inner ear, between the basilar and tectorial membranes. The actual sensory receptors are called inner hair cells. The outer hair cells serve other functions, such as sound amplification in the cochlea, and are not discussed in detail here.
01:13The Cochlea
The cochlea is a coiled structure in the inner ear that contains hair cells—the sensory receptors of the auditory system. Sound waves are transmitted to the cochlea by small bones attached to the eardrum called the ossicles, which vibrate the oval window that leads to the inner ear. This causes fluid in the chambers of the cochlea to move, vibrating the basilar membrane.
01:11The Auditory Ossicles
The auditory ossicles of the middle ear transmit sounds from the air as vibrations to the fluid-filled cochlea. The auditory ossicles consist of two malleus (hammer) bones, two incus (anvil) bones, and two stapes (stirrups), one on each side. These bones develop during the fetal stage and are the ones to ossify first. They are fully mature at birth and do not grow afterward.
The aptly named stapes look very much like a stirrup. The three ossicles are unique to mammals, and each plays a role in...
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01:16Anatomy of the Ear
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