Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells
| Autor: | Dalton McLean, William McLean, Xiaolei Yin, Danielle R. Lenz, Robert Langer, Albert S.B. Edge, Lin Lu, Jeffrey M. Karp |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, McLean, Will J., Yin, Xiaolei, Lu, Lin, Langer, Robert S |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Cellular differentiation Population Biology Article General Biochemistry Genetics and Molecular Biology Receptors G-Protein-Coupled Mice 03 medical and health sciences Hair Cells Auditory medicine otorhinolaryngologic diseases Animals Humans education Wnt Signaling Pathway lcsh:QH301-705.5 Cochlea Cell Proliferation Mammals education.field_of_study integumentary system Stem Cells LGR5 Wnt signaling pathway Cell Differentiation Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Synapses Immunology Hair cell sense organs Stem cell Transduction (physiology) Signal Transduction |
| Zdroj: | Elsevier Cell Reports, Vol 18, Iss 8, Pp 1917-1929 (2017) |
| Popis: | Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments. United States. National Institutes of Health (DE-013023) United States. National Institutes of Health (DC-007174) United States. National Institutes of Health (DC-013909) United States. National Institutes of Health (RR-00168) |
| Databáze: | OpenAIRE |
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