Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea

// Muhammad Waqas 1, 2, 3 * , Luo Guo 4, 5, * , Shasha Zhang 1, 2 , Yan Chen 4, 5 , Xiaoli Zhang 7 , Lei Wang 6 , Mingliang Tang 1, 2 , Haibo Shi 8 , Phillip I. Bird 9 , Huawei Li 4, 5, 6 , Renjie Chai 1, 2, 3 1 State Key Laboratory of Bioelectronics, Institute of Life Sciences, Southeast University, Nanjing, China 2 MOE Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, China 3 Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China 4 Department of Otorhinolaryngology, Hearing Research Institute, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China 5 Central Laboratory, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, China 6 Institutes of Biomedical Sciences, Fudan University, Shanghai, China 7 Department of Otolaryngology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China 8 Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China 9 Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia * These authors have contributed equally to this work Correspondence to: Renjie Chai, email: renjiec@seu.edu.cn Huawei Li, email: lihuawei63@gmail.com Keywords: Wnt signaling, Lgr5, cochlea, regeneration, proliferation Received: December 10, 2015 Accepted: March 28, 2016 Published: April 7, 2016 ABSTRACT Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future.