Mapping oto-pharyngeal development in a human inner ear organoid model
Creators
- 1. Indiana University
- 2. Leiden University Medical Center
- 3. Boston Children's Hospital
- 4. Harvard Medical School
Description
Inner ear development requires the coordination of cell types from
distinct epithelial, mesenchymal and neuronal lineages. Although we
have learned much from animal models, many details about human
inner ear development remain elusive. We recently developed an
in vitro model of human inner ear organogenesis using pluripotent
stem cells in a 3D culture, fostering the growth of a sensorineural
circuit, including hair cells and neurons. Despite previously
characterizing some cell types, many remain undefined. This study
aimed to chart the in vitro development timeline of the inner ear
organoid to understand the mechanisms at play. Using single-cell
RNA sequencing at ten stages during the first 36 days of
differentiation, we tracked the evolution from pluripotency to various
ear cell types after exposure to specific signaling modulators. Our
findings showcase gene expression that influences differentiation,
identifying a plethora of ectodermal and mesenchymal cell types. We
also discern aspects of the organoid model consistent with in vivo
development, while highlighting potential discrepancies. Our study
establishes the Inner ear Organoid Developmental Atlas (IODA),
offering deeper insights into human biology and improving inner ear
tissue differentiation.
Files
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