Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

PLoS One

Dhasakumar S. Navaratnam¹  Steven H. Kleinstein¹  Mohamed Uduman²  Jamie L. Duke³  Joseph Santos-Sacchi³  Corey S. Frucht⁴ 

[1] Department of Pathology, Yale School of Medicine, New Haven, Connecticut, United States of America;Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, United States of America;Interdepartmental Program in Computation Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America;Medical Scientist Training Program, Yale School of Medicine, New Haven, Connecticut, United States of America

关键词: MicroRNAs;    Gene expression;    Chickens;    Inner ear;    Transcription factors;    Epithelium;    Microarrays;    Hair;   

DOI  :  10.1371/journal.pone.0011502

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.Methodology/Principal Findings Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.Conclusions/Significance These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells.

【 授权许可】

CC BY