期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7613
关键词
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资金
- NIH-NCATS-CTSA [UL1 TR001085]
- Lucile Packard Foundation for Children's Health
- Child Health Research Institute
- National Basic Research Program of China [2012CB967904, 2012CB967900, 2015CB965000]
- National Natural Science Foundation of China [81470692]
- Natural Science Foundation from Jiangsu Province [BK20140620]
- Stanford University Medical Scholars Program
- Howard Hughes Medical Institute Medical Scholars Fellowship
- Swedish Research Council [C0657401, R01DC006471, P30CA21765]
- American Lebanese Syrian Associated Charities
- Office of Naval Research
- NIDCD Division of Intramural Research [1ZIADC000079]
- NIDCD/NIH [P30DC010363, K08DC011043, RO1DC013910]
- Department of Defense [W81XWH-14-1-0517]
- Akiko Yamazaki and Jerry Yang Faculty Scholar Fund
- American Hearing Research Foundation
- California Initiative in Regenerative Medicine [RN3-06529]
Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized beta-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration.
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