Year 3

How a mortal somatic cell can have its fate changed to become an immortal pluripotent stem cell is a fascinating area of biology in which the rules of this transformative event are still being established.  The pioneering work of Yamanaka, Gurden and Jaenisch have shown us that at least 4 transcription factors can drive this process.  However, the efficiency and predictability is astonishingly low, sometimes measuring in the 1/100 of a percentage.

My lab has been working on the hypothesis that part of the reprogramming process must involve a remodeling of the proteome and organelles.  Top our surprise, we submit to you a very interesting set of observations that indicate that one new rule for the reprogramming process is the transient induction of the endoplasmic reticulumn unfolded stress response (UPR^ER).  We find that the ER goes through a massive transition in form and function during remodeling that requires the UPR^ER.  Furthermore, we find that this induction is transient, essential and reduces the stochasticity found in the reprogramming process bringing the success rate of iPS formation upwards dramatically.  More importantly, we find the induction of the UPR^ER to be predictive of reprogramming success.  This point is perhaps one of the most novel findings that we submit since we find in a culture of genetically identical cells grown within the same dish have inherently different levels of UPR^ER induction.  We sorted based on the induction of the UPR^ER, we find that the highest inducers are the best at forming iPS cells.  The best part of all of these findings is that we can enhance this process using drugs that induce the UPR^ER, and this only has to be done during a certain period of the reprogramming process.