Indiana University-Purdue University Indianapolis (IUPUI) / Inner ear development requires the complex interaction of numerous cell
types arising from multiple embryologic origins. Current knowledge of inner ear
organogenesis is limited primarily to animal models. Although most mechanisms
of cellular development show conservation between vertebrate species, there are
uniquely human aspects of inner ear development which remain unknown.
Our group recently described a model of in vitro human inner ear
organogenesis using pluripotent stem cells in a 3D organoid culture system. This
method promotes the formation of an entire sensorineural circuit, including hair
cells, inner ear neurons, and Schwann cells. Our past work has characterized
certain aspects of this culture system, however we have yet to fully define all the
cell types which contribute to inner ear organoid assembly.
Here, our goal was to reconstruct a time-based map of in vitro
development during inner ear organoid induction to understand the
developmental elements captured in this system. We analyzed inner ear
organoid development using single-cell RNA sequencing at ten time points
during the first 36 days of induction.
We reconstructed the on-target progression of undifferentiated pluripotent
stem cells to surface ectoderm, pre-placodal, and otic epithelial cells, including
supporting cells, hair cells, and neurons, following treatment with FGF, BMP, and WNT signaling modulators. Our data revealed endogenous signaling pathwayrelated
gene expression that may influence the course of on-target differentiation.
In addition, we classified a diverse array of off-target ectodermal cell types
encompassing the neuroectoderm, neural crest, and mesenchymal lineages. Our
work establishes the Inner ear Organoid Developmental Atlas (IODA), which can
provide insights needed for understanding human biology and refining the guided
differentiation of in vitro inner ear tissue. / 2024-08-02
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/29734 |
| Date | 07 1900 |
| Creators | Steinhart, Matthew Reed |
| Contributors | Meyer, Jason S., Koehler, Karl R., Herbert, Brittney-Shea, Landreth, Gary E., Shearer, A. Eliot, Yates, Charles W. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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