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. Author manuscript; available in PMC: 2013 Jul 20.
Published in final edited form as: Kidney Int. 2009 Apr 1;75(11):1153–1165. doi: 10.1038/ki.2009.73

Figure 4.

Figure 4

Models of squamous metaplasia of the mouse urothelium induced by vitamin A deficiency. (a) Schematic diagram showing gradual expansion of the vitamin A deficiency-induced squamous metaplasia from the proximal urethra (PU) and the trigone (TG) region to the rest of the bladder (B). UR, ureter; K, kidney. (b–f) Models for various cellular mechanisms of bladder metaplasia. (b) The transdifferentiation model: A terminally differentiated cell (DC; square) can directly transform into a different kind of terminally differentiated cell (diamond). (c) The dedifferentiation-and-redifferentiation model: A terminally differentiated cell can revert back to an undifferentiated or stem cell, which can then differentiate along a different pathway yielding a distinct phenotype in response to environmental and/or mesenchymal changes (beige). (d) The pluripotent stem cell model: Under normal conditions, the pluripotent stem cells give rise to terminal differentiated cells of a particular phenotype; mesenchymal changes may induce such a stem cell to undergo an alternative pathway of differentiation. (e) The selective expansion model. The tissue contains two separate populations of stem cells: one of them (yellow) normally gives rise to the main phenotype, whereas the other lies dormant. Mesenchymal and/or environmental changes including alterations of the stem cell niche suppress the growth and differentiation of the originally dominant stem cell while activating the originally dormant stem cell (red) that now gives rise to a different phenotype. (f) The expansion and replacement model. The tissue contains two separate cell lineages that occupy different domains separated by well-defined boundaries. Mesenchymal and/or environmental changes such as vitamin A deficiency favor the expansion of one cell lineage over another, thus allowing one cell type to expand and invade into another cell lineage’s domain. This last model can best explain existing data on urothelial keratinizing squamous metaplasia that is induced by vitamin A deficiency. (d–f) The parallel red bars denote that the process/pathway is blocked. SC, stem cell. (adapted from Ref. 60).