These details gleaned from this regenerative process in the mouse organoid provides insights into how mammalian supporting cells could be reprogrammed into hair cells.
Cochlear Organoids Reveal How Supporting Cells Differentiate Into Hair Cells
Genetic Reprogramming Converts Nonsensory Cells into Sensory Cells in the Mature Cochlea
We have artificially expressed three key hair cell fate promoting proteins in nonsensory cells of adult mice, and found that a significant number of these cells will convert into cells resembling hair cells. This offers a potential strategy for hair cell regeneration.
Mathematical Analysis of Zebrafish Cell Shape Shows Connection With Cell Function
Our results demonstrate the utility of using 3D cell shape features to characterize, compare, and classify cells in a living, developing organism.
An Essential Signaling Cascade for Hair Cell Regeneration in Birds
This work provides a new starting point to investigate the natural triggers of hair cell regeneration in birds. We also identified novel genes that drive hair cell regeneration in the chicken inner ear. These novel genes will be key for investigating their potential role in triggering a change in supporting cells in mammals, in the damaged mouse or human cochlea.
Mouse Studies Tune Into Hearing Regeneration
In the non-sensory supporting cells of the inner ear, key genes required for conversion to sensory cells are shut off through a process known as epigenetic silencing. By studying how the genes are shut off, we begin to understand how we might turn them back on to regenerate hearing.
A Boost to Inner Ear Organoid Development
This paper explored the potential of the stem cell-derived inner ear organoid system for studying early mammalian placode development. The results will benefit future inner ear organoid applications, such as high-throughput drug screening and cell therapy.
Cell-Type Identity of the Chick Balance Organ
We have now identified the first events that lead to proliferative hair cell regeneration in birds, which provides new leads that can be translated to mice and ultimately to humans.
Increasing Our Understanding of Avian Hair Cell Regeneration
We provide evidence that in the regenerating basilar papilla, the expression of immune-related genes is tightly controlled, such that four days after damage, they are no longer expressed in newly regenerated hair cells. This is important because the JAK/STAT signaling pathway is highly potent, leading to inflammation, cytokine storms, and fibrosis.
Cochlear Organoids Reveal HIC1’s Role in Hair Cell Differentiation
Emerging Research Grants scientist Dunia Abdul-Aziz, M.D., of Harvard Medical School and Mass Eye and Ear coauthored a study that reveals how the gene Atoh1 in the cochlea can be repressed by the protein HIC1, inhibiting hair cell differentiation. It also demonstrates the power of combining the organoid model with the genetic toolkit to study key regulators of hair cell differentiation, which may help advance the understanding of hair cell development and regeneration.
A Combination of Genes to Enhance Hair Cell Regeneration in the Adult Mammalian Cochlea
Due to the lack of spontaneous regeneration, the hearing loss caused by hair cell loss is permanent. One way to envision future biological/medical repair of the hair cell-depleted inner ear is to medically induce the generation of new hair cells.