title: Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages.
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.
authors.affiliation: 1] State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China [2] School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Helen He
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chu
authors.affiliation: School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The MOE Key Laboratory of Model Animal for Disease Study and the Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The MOE Key Laboratory of Model Animal for Disease Study and the Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Life Science, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory of Oncogenes and Related Genes, Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China [2] School of Biomedical Engineering &Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D002455:Cell Division; D019070:Cell Lineage; D016764:Cell Polarity / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011467:Prostate / Q000166:cytology* / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D000077022:Survivin; D015534:Trans-Activators / Q000235:genetics
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D000077022:Survivin; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse