Wnt-responsive Lgr5-expressing stem cells are hair cell progenitors in the cochlea.
Auditory hair cells are surrounded on their basolateral aspects by supporting cells, and these two cell types together constitute the sensory epithelium of the organ of Corti, which is the hearing apparatus of the ear. We show here that Lgr5, a marker for adult stem cells, was expressed in a subset of supporting cells in the newborn and adult murine cochlea. Lgr5-expressing supporting cells, sorted by flow cytometry and cultured in a single-cell suspension, compared with unsorted cells, displayed an enhanced capacity for self-renewing neurosphere formation in response to Wnt and were converted to hair cells at a higher (>10-fold) rate. The greater differentiation of hair cells in the neurosphere assay showed that Lgr5-positive cells had the capacity to act as cochlear progenitor cells, and lineage tracing confirmed that Lgr5-expressing cells accounted for the cells that formed neurospheres and differentiated to hair cells. The responsiveness to Wnt of cells with a capacity for division and sensory cell formation suggests a potential route to new hair cell generation in the adult cochlea.
Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fuxin
F
Shi
Judith S
JS
Kempfle
Albert S B
AS
Edge
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002771:Cholera / Q000145:classification* / Q000188:drug therapy / Q000378:metabolism; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006198:Hair Cells, Auditory / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*; D013820:Thermolysin / Q000494:pharmacology; D019699:Thrombospondins / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics; D060509:Wnt3A Protein / Q000494:pharmacology*
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D000081412:Myosin VIIa; D009218:Myosins; D011506:Proteins; D012333:RNA, Messenger; D022661:RNA, Untranslated; D043562:Receptors, G-Protein-Coupled; D055748:SOXB1 Transcription Factors; D013820:Thermolysin; D019699:Thrombospondins; D060509:Wnt3A Protein; C500943:Atoh1 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C493597:Lgr5 protein, mouse; C000631456:Myo7a protein, mouse; C518903:RSPO1 protein, mouse; C527783:Sox2 protein, mouse; C555511:Wnt3a protein, mouse