title: Stemness of the organ of Corti relates to the epigenetic status of Sox2 enhancers.
abstract: In the adult mammalian auditory epithelium, the organ of Corti, loss of sensory hair cells results in permanent hearing loss. The underlying cause for the lack of regenerative response is the depletion of otic progenitors in the cell pool of the sensory epithelium. Here, we show that an increase in the sequence-specific methylation of the otic Sox2 enhancers NOP1 and NOP2 is correlated with a reduced self-renewal potential in vivo and in vitro; additionally, the degree of methylation of NOP1 and NOP2 is correlated with the dedifferentiation potential of postmitotic supporting cells into otic stem cells. Thus, the stemness the organ of Corti is related to the epigenetic status of the otic Sox2 enhancers. These observations validate the continued exploration of treatment strategies for dedifferentiating or reprogramming of differentiated supporting cells into progenitors to regenerate the damaged organ of Corti.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hearing Research Center Tübingen, University of Tübingen Medical Center, Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Waldhaus
authors.forename: Jelka
authors.initials: J
authors.lastname: Cimerman
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Mathias
authors.initials: M
authors.lastname: Ehrich
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Hubert
authors.initials: H
authors.lastname: Löwenheim
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016000:Cluster Analysis; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic; D004815:Epidermal Growth Factor / Q000494:pharmacology; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000378:metabolism; D009925:Organ of Corti / Q000196:embryology / Q000378:metabolism*; D011957:Receptors, Opioid / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000094942:Nociceptin Receptor
chemical_list: D011957:Receptors, Opioid; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D004815:Epidermal Growth Factor; D000094942:Nociceptin Receptor; C000722287:Oprl1 protein, mouse