Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing
Year: 2016
Type: article
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.
Source: PLoS ONE
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: U.S. Department of Defense, Hearing Health Foundation, National Institutes of Health, Comisión Nacional de Investigación Científica y Tecnológica, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1194650153, Baylor-UT Houston Center for AIDS Research, G1504377518, Identifying the Atoh1 targetome in hair cells with deep sequencing, G1631989702, BD Biosciences Special Order LSRII, G4119534169, G4182736573, Baylor Intellectual and Developmental Disabilities Research Center, G5403410128, G5850682332, Genetic Regulation of Cochlear Development, G7090991247, G7757145121, G8733582291, G8756068386, G8919310273, G9000066967, G9000154505, G9000198215, G9000240210, Baylor College of Medicine Cancer Center - Cancer Center Support Grant, Enhancing Atoh1 function in hair cell regeneration
OpenAlex ID: W2559829696