Imaging Asymmetric Division in Stem Cells and Cancer.

While it has long been speculated that mammalian stem cells undergo asymmetric and symmetric division, whether this actually occurs has not been clearly demonstrated. We have used a transgenic Notch reporter mouse, in which the GFP status of a cell acts as a sensor for the differentiated state, to image how mammalian hematopoietic stem cells divide and respond to signals during growth, differentiation, and oncogenic transformation. We show that mammalian hematopoietic stem cells have the ability to undergo both symmetric and asymmetric divisions and that the balance between these divisions is not hardwired in precursors but, instead, responsive to extrinsic and intrinsic cues. In addition, we show that oncoproteins can also influence a cell’s choice between symmetric and asymmetric division. Cumulatively, this work not only establishes a novel system in which division of early hematopoietic precursor cells can not only be tracked in real time, but also indicates that the distribution of symmetric and asymmetric division can be modulated in response to the microenvironment and subverted by oncogenes.