Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells
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McLean-2017-Clonal Expansion of Lgr5-Positive.pdf
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Author(s)
Lenz, Danielle R.
McLean, Dalton
Karp, Jeffrey M.
Edge, Albert S.B.
McLean, Will J.
Yin, Xiaolei
Lu, Lin
Langer, Robert S
Date Issued
February 2017
Journal
Cell Reports
Publisher
Elsevier
Citation
McLean, Will J.; Yin, Xiaolei; Lu, Lin; Lenz, Danielle R.; McLean, Dalton; Langer, Robert; Karp, Jeffrey M. and Edge, Albert S.B. “Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells.” Cell Reports 18, no. 8 (February 2017): 1917–1929 © 2017 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
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
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2017.01.066
