Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages

Jia Wang, Helen He Zhu, Mingliang Chu, Yunying Liu, Chenxi Zhang, Geng Liu, Xiaohang Yang, Ru Yang and Wei-Qiang Gao ()
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Jia Wang: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Helen He Zhu: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Mingliang Chu: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Yunying Liu: School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University
Chenxi Zhang: The MOE Key Laboratory of Model Animal for Disease Study and the Model Animal Research Center, Nanjing University
Geng Liu: The MOE Key Laboratory of Model Animal for Disease Study and the Model Animal Research Center, Nanjing University
Xiaohang Yang: College of Life Science, Zhejiang University
Ru Yang: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Wei-Qiang Gao: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Although symmetrical and asymmetrical divisions of stem cells have been extensively studied in invertebrate and mammalian neural epithelia, their role remains largely unknown in mammalian non-neural epithelial development, regeneration and tumorigenesis. Here, using basal and luminal cell-specific markers and cell lineage tracing transgenic mice, we report that in developing prostatic epithelia, basal and luminal cells exhibit distinct division modes. While basal cells display both symmetric and asymmetric divisions leading to different cell fates, luminal cells only exhibit symmetrical divisions. Examination of cell division modes in prostate-specific Pten-null mice indicates that both luminal and basal cells can be cellular origins for prostate cancer. Furthermore, analysis of Sox2-expressing cells in p63 and Pten-null mice suggests that basal cells contribute to the luminal population and tumorigenesis. These findings provide direct evidence for the existence of a hierarchy of epithelial cell lineages during prostate development, regeneration and tumorigenesis.

Date: 2014
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DOI: 10.1038/ncomms5758

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