Advanced Concepts in Stem Cell Biology

Reprogramming Cell Fate
1. Nuclear Transfer
  1. Somatic cell nucleus is injected into an enucleated oocyte, which are then fused together
    1. Reprograms the nucleus
      1. Resulting embryo generates an identical clone of the donor organism
        e.g. tadpoles, Dolly the sheep
2. Cell Fusion
  1. Two cell types are combined together
    1. Just the cytoplasm fused
    2. If DNA replication and cell division does not occur, a binucleated heterokaryon is produced
      1. If it does, a synkaryon is produced instead
        Can be euploid (equal number of chromosomes - fuse cells from the same species)
        Or aneuploid (abnormal number of chromosomes - fuse cells from different species)
3. Transcription-Factor Transduction
  1. TFs such as c-Myc, Oct4, Sox2 and Klf4 activate pluripotency in a somatic cell
    1. Causes it to divide into induced pluripotent stem cells (iPS cells)
      1. Uses
        Patient-specific cell therapy
        Drug screening
        Human disease modelling
Lineage Specifiers
1. Suggested that pluripotency factors such as Oct4 and Sox2 also function to specify a lineage during ESC differentiation
  1. Overexpression of certain factors leads to differentiation of a specific lineage
2. Oct4 specifies the mesoderm
3. Sox2 specifies the neuroectoderm
4. Extrinsic cytokine signalling
  1. Mechanism which allows control of the expression of the various pluripotency factors which determine cell fate
  2. ESCs remain undifferentiated due to all of the key pluripotency factors being expressed at similar levels
    1. No factor becomes dominant, and so differentiation does not occur
  3. Key to stem cells self-renewing and maintaining of their undifferentiated state

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Advanced Concepts in Stem Cell Biology

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