Stem Cells and Asymmetric Cell Division

Abstract

Asymmetric stem cell division is a fundamental process used to generate cellular diversity and to provide a source of new cells in developing and adult organisms. Asymmetric stem cell division leads to another stem cell via self-renewal, and a second cell type which can be either a differentiating progenitor or a postmitotic cell. Experimental studies in model organisms including the nematode Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the laboratory mouse, Mus musculus, have identified interrelated mechanisms that regulate asymmetric stem cell division from polarity formation and mitotic spindle orientation to asymmetric segregation of cell fate determinants and growth control. These mechanisms are mediated by evolutionary conserved molecules including Aurora-A, aPKC, Mud/NuMa, Lgl, Numb and Brat/TRIM-NHL, which in turn regulate a binary switch between stem cell self-renewal and differentiation. The mechanistic insights into asymmetric cell division have enhanced our understanding of stem cell biology and are of major therapeutic interest for regenerative medicine as asymmetrically dividing stem cells provide a powerful source for targeted cell replacement and tissue regeneration.