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minus = plus

People are so busy working on eliminating genes that are necessary for inducible pluripotent cell (iPS) production. The less, the better! We were so excited to see this “4-way” cocktail to be stripped to a single component, Oct4, to drive neuronal crest cells to pluripotent cell in mice [1]and human [2](pdf [3]).

Given extremely low efficiency of iPS induction, any improvement on the method is regarded as a huge leap for this technology. Plus or minus, it’s the problem. Yamanaka [4] and 4 other groups [5] found if p53 pathway is screwed up on top of their home-made “4-way” cocktail and cells are released from immortalilzation restriction, iPS induction efficiency increased by 100-fold. Whoa!! And they all get Nature publications. Whoa!!!

But, guys, let’s sit back and stay cool. Actually, increased induction efficiency of iPS by inactivating p53 is a trade-off of DNA integrity. In like manner, handicapping INK4 (p16)/ARF gave similar boosting for iPS induction efficiency and speed [6]. As p53 works as a loyal guardian for DNA damage, inactivating p53 can also make induction of iPS from suboptimal cells [7], such as older cell and DNA-damage preloaded cell, possible.

One day, we’ll be confront with a common dilemma: cardiac disease or cancer, Alzheimer’s disease or cancer, spinal injury or cancer, to die soon or quick, to be or not to be…