What are the principles of stem cell engineering?
The roles of the reprogramming factors Oct4, Sox2 and Klf4 in resetting the somatic cell epigenome during induced pluripotent stem cell generation


  Current reprogramming technology, pioneered by Takahashi and Yamanaka
  1, was built on several seminal advances in the field of
  developmental biology. First, nuclear transfer experiments
  demonstrated that a somatic cell nucleus could be epigenetically reset
  to an early developmental state [2]. Second, cell culture conditions
  were developed that allowed for the isolation and culture of
  pluripotent cells, termed embryonic stem (ES) cells, from the inner
  cell mass of the human and mouse blastocyst [3,4]. Finally, study of
  these cells and of early embryonic development led to the
  identification of factors that were ultimately able to reprogram mouse
  embryonic fibroblasts (MEFs) to the iPS cell state when ectopically
  expressed, albeit at low frequency.
  
  Reprogramming of somatic cells is a multistep process that culminates
  in the expression of pluripotency genes such as Nanog. Although
  morphological changes occur at early and intermediate stages of
  reprogramming, pluripotency gene expression is only induced during the
  late stage and indicates faithful reprogramming.
  
  The core reprogramming cocktail, consisting of the transcription
  factors Oct4, Sox2 and Klf4 can be augmented by the
  addition of factors that enhance the efficiency of iPS cell
  generation


Its a multistep process in which much research is still needed,


  The frequency with which somatic cells convert to iPS cells is
  typically below 1%. Therefore, much effort has gone into improving
  reprogramming.


specially to increase efficiency of iPS cell generation


  The ability of cells to pass through the cell cycle has also been
  shown to be an important determinant of reprogramming efficiency.
  Knockdown or gene deletion of p53, p21 or proteins expressed from the
  Ink4/Arf locus allows cells undergoing reprogramming to avoid the
  activation of cell cycle checkpoints and cellular senescence, leading
  to greater iPS cell formation [21],24-27].


Gene expression changes during reprogramming