Dataset Information

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

ABSTRACT: Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both in vitro and in vivo and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated Lgr5+ progenitors and Lgr5- SCs from Lgr5-EGFP-CreERT2/Sox2-CreERT2/Rosa26-tdTomato mice via flow cytometry. As expected, we found that Lgr5+ progenitors had significantly higher proliferation and HC regeneration ability than Lgr5- SCs. Next, we performed RNA-Seq to determine the gene expression profiles of Lgr5+ progenitors and Lgr5- SCs. We analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors and Lgr5- SCs, and we found 8 cell cycle genes, 9 transcription factors, and 24 cell signaling pathway genes that were uniquely expressed in one population but not the other. Last, we made a protein-protein interaction network to further analyze the role of these differentially expressed genes. In conclusion, we present a set of genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these might serve as potential new therapeutic targets for HC regeneration.

SUBMITTER: Cheng C

PROVIDER: S-EPMC5405134 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

Cheng Cheng C Guo Luo L Lu Ling L Xu Xiaochen X Zhang ShaSha S Gao Junyan J Waqas Muhammad M Zhu Chengwen C Chen Yan Y Zhang Xiaoli X Xuan Chuanying C Gao Xia X Tang Mingliang M Chen Fangyi F Shi Haibo H Li Huawei H Chai Renjie R

Frontiers in molecular neuroscience 20170426

Cochlear supporting cells (SCs) have been shown to be a promising resource for hair cell (HC) regeneration in the neonatal mouse cochlea. Previous studies have reported that Lgr5+ SCs can regenerate HCs both <i>in vitro</i> and <i>in vivo</i> and thus are considered to be inner ear progenitor cells. Lgr5+ progenitors are able to regenerate more HCs than Lgr5- SCs, and it is important to understand the mechanism behind the proliferation and HC regeneration of these progenitors. Here, we isolated ...[more]

PMID: 28491023

Similar Datasets

Project description:Hair cell (HC) loss is irreversible because only very limited HC regeneration has been observed in the adult mammalian cochlea. Wnt/?-catenin signaling regulates prosensory cell proliferation and differentiation during cochlear development, and Wnt activation promotes the proliferation of Lgr5+ cochlear HC progenitors in newborn mice. Similar to Lgr5, Lgr6 is also a Wnt downstream target gene. Lgr6 is reported to be present in adult stem cells in the skin, nail, tongue, lung, and mammary gland, and this protein is very important for adult stem cell maintenance in rapidly proliferating organs. Our previous studies showed that Lgr6+ cells are a subpopulation of Lgr5+ progenitor cells and that both Lgr6+ and Lgr5+ progenitors can generate Myosin7a+ HCs in vitro. Thus we hypothesized that Lgr6+ cells are an enriched population of cochlear progenitor cells. However, the detailed distinctions between the Lgr5+ and Lgr6+ progenitors are unclear. Here, we systematically compared the proliferation, HC differentiation, and detailed transcriptome expression profiles of these two progenitor populations. We found that the same number of isolated Lgr6+ progenitors generated significantly more Myosin7a+ HCs compared to Lgr5+ progenitors; however, Lgr5+ progenitors formed more epithelial colonies and more spheres than Lgr6+ progenitors in vitro. Using RNA-Seq, we compared the transcriptome differences between Lgr5+ and Lgr6+ progenitors and identified a list of significantly differential expressed genes that might regulate the proliferation and differentiation of these HC progenitors, including 4 cell cycle genes, 9 cell signaling pathway genes, and 54 transcription factors. In conclusion, we demonstrate that Lgr6+ progenitors are an enriched population of inner ear progenitors that generate more HCs compared to Lgr5+ progenitors in the newborn mouse cochlea, and the our research provides a series of genes that might regulate the proliferation of progenitors and HC generation.

Dataset Information

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

Publications

Characterization of the Transcriptomes of Lgr5+ Hair Cell Progenitors and Lgr5- Supporting Cells in the Mouse Cochlea.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets