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Published September 20, 2023 | Version 1
Software Open

Mapping oto-pharyngeal development in a human inner ear organoid model

  • 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.

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