title: Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing.
abstract: Neonatal mouse cochlear supporting cells have a limited ability to divide and trans-differentiate into hair cells, but this ability declines rapidly in the two weeks after birth. This decline is concomitant with the morphological and functional maturation of the organ of Corti prior to the onset of hearing. However, despite this association between maturation and loss of regenerative potential, little is known of the molecular changes that underlie these events. To identify these changes, we used RNA-seq to generate transcriptional profiles of purified cochlear supporting cells from 1- and 6-day-old mice. We found many significant changes in gene expression during this period, many of which were related to regulation of proliferation, differentiation of inner ear components and the maturation of the organ of Corti prior to the onset of hearing. One example of a change in regenerative potential of supporting cells is their robust production of hair cells in response to a blockade of the Notch signaling pathway at the time of birth, but a complete lack of response to such blockade just a few days later. By comparing our supporting cell transcriptomes to those of supporting cells cultured in the presence of Notch pathway inhibitors, we show that the transcriptional response to Notch blockade disappears almost completely in the first postnatal week. Our results offer some of the first molecular insights into the failure of hair cell regeneration in the mammalian cochlea.
authors.affiliation: Department of Otolaryngology, Hospital Clínico Universidad de Chile and Interdisciplinary Program of Physiology and Biophysics ICBM Universidad de Chile, Santiago, Chile.|Department of Otolaryngology, Clínica Alemana de Santiago, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Maass
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Rende
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.|The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Ying-Wooi
authors.initials: YW
authors.lastname: Wan
authors.affiliation: Department of Otolaryngology, Hospital Clínico Universidad de Chile and Interdisciplinary Program of Physiology and Biophysics ICBM Universidad de Chile, Santiago, Chile.
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Cantellano
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Joanna S T
authors.initials: JS
authors.lastname: Asprer
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Jen
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Renée K
authors.initials: RK
authors.lastname: Edlund
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.|The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, United States of America.
authors.forename: Zhandong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.|Program in Developmental Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.|Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, United States of America.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Groves
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003051:Cochlea / Q000502:physiology*; D007758:Ear, Inner / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D006198:Hair Cells, Auditory / Q000502:physiology*; D006309:Hearing / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D009925:Organ of Corti / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics*; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D051880:Receptors, Notch