Generating Cell Fate Diversity, with or without a Permanent Niche

Life is a succession of cell divisions. For multicelled beings, diversity in the fate of a cell’s progeny is essential for orderly tissue formation and specialized function. Knowledge of how kindred cells diverge in fate is essential for understanding organ formation and function, stem cell and tissue regeneration, immunity, and cancer. At least two distinct mechanisms, representing the cellular versions of “nature” versus “nurture,” can promote daughter cell diversity (Fig. 1). After inception, identically born daughter cells can be nurtured to adopt different fates by encountering distinct signals in their environments. There also exists an evolutionarily conserved mechanism, called asymmetric cell division, whereby a dividing cell imparts unequal inheritance of its components to its two daughter cells, making them different from inception (Betschinger and Knoblich 2004; Knoblich 2008). Scattered instances of asymmetric cell division have been described across evolution for generating specialized cells within an organ and for enabling the regeneration of progenitor cells in tissues that require continuous production of differentiated progeny, such as skin (Lechler and Fuchs 2005). Asymmetric cell division has typically been associated with tissues that already possess intrinsic apical-basal polarity. In those situations, the constitutive attachment of a cell to the basement membrane provides a framework that allows the daughter attached to the basement membrane to retain the stem cell fate, Asymmetric Division and Stem Cell Renewal without a Permanent Niche: Lessons from Lymphocytes