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Dev Cell. 2013 Sep 16;26(5):469-482. doi: 10.1016/j.devcel.2013.07.017. Epub 2013 Aug 29.

Retinoid signaling in progenitors controls specification and regeneration of the urothelium.

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Columbia University, Depts. of Urology, Genetics & Development and Pathology 1130 St. Nicholas Avenue, New York NY, USA.
Columbia University, Department of Pathology, 630 West 168th Street, New York, NY, USA.
IGBMC, CNRS UMR7104/ INSERM U964, Université de Strasbourg, Collège de France, B.P. 10142, ILLKIRCH Cedex, FRANCE.
Department of Cell Biology, New York University Medical School, 550 First Avenue, New York, NY, USA.
Division of Biomedical Informatics 3333 Burnet Ave., MLC 7024 Cincinnati, OH 45229.
Boston Children's Hospital, Urological Diseases Research Center, Enders Research Building, 300, Longwood Avenue, Boston, MA 02115 USA.
Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Contributed equally


The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome.

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