Cell turnover and adult tissue homeostasis

Cell turnover and adult tissue homeostasis: from humans to planarians.  Annu. Rev. Genet. 41, 83–105 (2007)

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Perhaps the most significant distinction between developing and adult tissues concerns the general degree of uniformity observed among constituent cells.  In developing systems such as Drosophila imaginal discs, nearly all of the cells are dividing and can be eliminated by cell death if their rate of division differs substantially from that of their neighbors.  In most adult systems, on the other hand, only stem cells and their transiently amplifying descendants undergo division and cell death occurs in postmitotic differentiated cells.  By definition, strictly cell-autonomous controls cannot synchronize the behavior of these distinct populations, arguing for the relative importance of cell-nonautonomous controls in adult tissue homeostasis.  Such extrinsic mechanisms must be significantly different than those underlying developmental phenomena like cell competition.  For example, the specific basis for cellular demise in competing cells, a slow rate of division, has no relevance for postmitotic cells in adult organs.  Moreover, the coincidence of patterning and growth in developing tissues has allowed some molecules like Dpp to be co-opted for use in both processes.  This duality might not apply to fully patterned adult tissues.

Despite these and other differences, there may be some general principles governing metazoan tissue dynamics throughout life.  For example, the notion that cells might be subject to some form of competition as a means of determining cellular “fitness” is not unique to Drosophila.  Competitive phenomena have also been observed in the social amoeba Dictyostelium discoideum, mice, and bacteria.  And adult stem cells in the murine germline and hematopoietic system appear to compete for access to niches.  Given the widespread occurrence of competition between individual cells or groups of cells throughout evolution, it is possible that these types of processes might control cell number during adult cell turnover.  Martin Raff has proposed one such model: “if a given level of survival factor supports a certain number of cells of a particular type, any increase of these cells above this number would stiffen the competition and thereby tend to cause enough cells to die to return the cell number to its original value; a fall in cell number would have the reverse effect.”