06: iPSCs

• reprogramming = reversal of differentiation
• yamanaka factors = oct4, sox2, klf4 and c-myc
• oct4 is a homeodomain transcription factor encoded for by the Pou5f1 gene

  • needs tight regulation for pluripotency
• sox2 and oct4 bind to adjacent sites on DNA to co-stimulate binding
• sox2, oct4 and nanog create super-enhancer domains of key genes to determine embryonic stem cell identity
• klf4 = zinc-finger containing transcription factor that controls expression of cell cycle regulatory genes

  • activation = cdh1
  • repression = p53
• c-myc is a proto-oncogene and a transcription factor

  • upregulates genes associated with dna replication and down regulates genes for cell adhesion
  • dispensable but increases efficiency
• improving reprogramming:

  • use retrovirus to deliver reprogramming genes to the cell
  • include nanog with yamanaka factors to increase efficiency
  • use another gene instead of c-myc as this can cause cancer
  • use urine cells - non-invasive
• we can create an iPSC from a diseased cell, repair the genome and then direct differentiation back into original cell and transplant it into the patient, leading to amelioration of the disease