Polyploid Superficial Cells that Maintain the Urothelial Barrier Are Produced via Incomplete Cytokinesis and Endoreplication

The urothelium is an epithelia barrier lined by a luminal layer of binucleated, octoploid, superficial cells. Superficial cells are critical for production and transport of uroplakins, a family of proteins that assemble into a waterproof crystalline plaque that helps protect against infection and to...

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Published inCell reports (Cambridge) Vol. 25; no. 2; pp. 464 - 477.e4
Main Authors Wang, Jia, Batourina, Ekatherina, Schneider, Kerry, Souza, Spenser, Swayne, Theresa, Liu, Chang, George, Christopher D., Tate, Tiffany, Dan, Hanbin, Wiessner, Gregory, Zhuravlev, Yelena, Canman, Julie C., Mysorekar, Indira U., Mendelsohn, Cathy Lee
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 09.10.2018
Elsevier
Subjects
Animals
Cell Differentiation
Cell Proliferation
Cells, Cultured
Cytokinesis
Endoreduplication
endoreplication
epithelial barrier
Female
Male
Mice
Mitosis
Polyploidy
regeneration
urothelium
Urothelium - injuries
Urothelium - physiopathology
polyploidy
epithelial barrier
regeneration
urothelium
endoreplication
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Summary:The urothelium is an epithelia barrier lined by a luminal layer of binucleated, octoploid, superficial cells. Superficial cells are critical for production and transport of uroplakins, a family of proteins that assemble into a waterproof crystalline plaque that helps protect against infection and toxic substances. Adult urothelium is nearly quiescent, but rapidly regenerates in response to injury. Yet the mechanism by which binucleated, polyploid, superficial cells are produced remains unclear. Here, we show that superficial cells are likely to be derived from a population of binucleated intermediate cells, which are produced from mononucleated intermediate cells via incomplete cytokinesis. We show that binucleated intermediate and superficial cells increase DNA content via endoreplication, passing through S phase without entering mitosis. The urothelium can be permanently damaged by repetitive or chronic injury or disease. Identification of the mechanism by which superficial cells are produced may be important for developing strategies for urothelial repair. [Display omitted] •Binucleated S-cells are critical for maintaining the urothelial barrier•S-cells derive from tetraploid I-cells that form via incomplete cytokinesis•Binucleated I- and S-cells increase ploidy via endoreplication•Polyploidy may enable the urothelium to efficiently adjust to environmental changes Binucleated superficial cells are critical for urothelial barrier function. Wang et al. show that they derive from binucleated intermediate cells that form via incomplete cytokinesis. Both superficial and intermediate cells increase ploidy via endoreplication, a feature likely to be important for repair and response to environmental changes.
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AUTHOR CONTRIBUTIONS
J.W. performed most of the immunostaining analysis. J.W., S.S., T.T., and C.L. analyzed the DNA content. J.W., G.W., H.D., and C.D.L. performed the CPP experiments and analyzed the CPP data. E.B. developed the organotypic culture, and T.S. helped with acquisition/processing of real-time images. K.S. and performed UTI experiments. G.W. and J.W. performed the pulse-chase experiments. Y.Z., K.S., J.W., and C.L.M. quantified data from experiments and performed statistical analysis. Y.Z., J.C.C., and C.M. generated figures. C.L.M., Y.Z., and J.W. wrote the manuscript and assembled the figures. I.U.M., J.C.C., Y.Z., and C.L.M. worked on revisions and responses to reviewer comments. C.L.M. supervised the experiments and organized the study.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.09.042