Generation of inner ear hair cells by direct lineage conversion of primary somatic cells
| Autor: | Chichou Huang, Suhasni Gopalakrishnan, Neil Segil, Louise Menendez, Litao Tao, Juan Llamas, Justin K. Ichida, Haoze V Yu, Alexander L Markowitz, Radha Kalluri, Xizi Wang, James Lee, Talon Trecek |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Tail
0301 basic medicine ATOH1 inner ear Mouse QH301-705.5 Science ototoxin Mice Transgenic Biology Regenerative medicine General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine medicine otorhinolaryngologic diseases Animals Cell Lineage Inner ear Biology (General) Hair Cells Auditory Inner General Immunology and Microbiology General Neuroscience Regeneration (biology) screening Labyrinth Supporting Cells reprogramming General Medicine Fibroblasts Stem Cells and Regenerative Medicine Embryonic stem cell Cell biology 030104 developmental biology medicine.anatomical_structure regeneration biology.protein Medicine Hair cell sense organs Stem cell sensory hair cell Reprogramming 030217 neurology & neurosurgery Research Article Developmental Biology Transcription Factors |
| Zdroj: | eLife, Vol 9 (2020) eLife |
| Popis: | The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing. eLife digest Worldwide, hearing loss is the most common loss of sensation. Most cases of hearing loss are due to the death of specialized hair cells found deep inside the ear. These hair cells convert sounds into nerve impulses which can be understood by the brain. Hair cells naturally degrade as part of aging and can be damaged by other factors including loud noises, and otherwise therapeutic drugs, such as those used in chemotherapy for cancer. In humans and other mammals, once hair cells are lost they cannot be replaced. Hair cells have often been studied using mice, but the small number of hair cells in their ears, and their location deep inside the skull, makes it particularly difficult to study them in this way. Scientists are seeking ways to grow hair cells in the laboratory to make it easier to understand how they work and the factors that contribute to their damage and loss. Different cell types in the body are formed in response to specific combinations of biological signals. Currently, scientists do not have an efficient way to grow hair cells in the laboratory, because the correct signals needed to create them are not known. Menendez et al. have now identified four proteins which, when activated, convert fibroblasts, a common type of cell, into hair cells similar to those in the ear. These proteins are called Six1, Atoh1, Pou4f3 and Gfi1. Menendez et al. termed the resulting cells induced hair cells, or iHCs for short, and analyzed these cells to identify those characteristics that are similar to normal hair cells, as well as their differences. Importantly, the iHCs were found to be damaged by the same chemicals that specifically harm normal hair cells, suggesting they are useful test subjects. The ability to create hair cells in the laboratory using more easily available cells has many uses. These cells can help to understand the normal function of hair cells and how they become damaged. They can also be used to test new drugs to assess their success in preventing or reversing hearing loss. These findings may also lead to genetic solutions to curing hearing loss. |
| Databáze: | OpenAIRE |
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