The expression of four transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can convert a fully differentiated cell into iPSCs. This cell fate conversion occurs, on average, in less than one in a thousand cells. Why are the great majority of OSKM-expressing cells fail to become iPSCs? Are there specific properties that enable the rare 0.1% of cells to adopt a new identity? We imaged thousands of cells over days and captured some of these rare cells from when they were blood cells to becoming iPSCs. 

Zooming in on one of the rare cells (tracked by the yellow arrow). Cells become GFP+ when they become iPSCs. 

Our ability to capture and visualize this rare cell fate conversion event offered unique insights into how cell fate might be controlled. One of the earliest features we noted about these cells is that they undergo very rapid cell cycle. For specific blood progenitors naturally existing in this fast cycling state, transitioning into iPSCs is extraordinarily fast and efficient. We termed these blood progenitors the privileged cells. The movie above shows a privileged cell changing from a blood fate into pluripotency. 

Now that we know one of the features these rare cells display is an ultrafast cell cycle, we are moving on to investigate how the rapid cell cycle dynamics is contributing to cell fate alteration. Some of our thoughts are discussed here.

Additional surprising features of these rare cells are being investigated in detail. We are also designing new ways to identify these rare cells. Stay tuned for our research update!