| dc.description.abstract | The differentiation of stem cells in a controlled fashion is essential to achieve a predefined
daughter cell types required for research or regenerative therapies. Transcription factors play a
key role in switching cellular differentiation fate in-vivo, at the initiation of the neuro or glial cell
fate specification phase in rodents and humans. The study aimed to assess if stem cell
differentiation can experimentally be manipulated using expression of cDNA of regulatory
homeodomain transcription factors Olig2, Nkx2,2, or Ngn2 in-vitro mirroring the in-vivo
development. Mouse embryonic stem (ES) cells and human foetal neural stem (FNS) cells were
cultured according to standard protocol. pIRES plasmid vector system with Olig2 transcription
factor expression, with or without the co-transcription factor Nkx2.2 (or Ngn 2), were created
using molecular biological techniques and introduced into differentiating stem cells. Using
biomarkers, final cell fates were compared with one another, including a placebo version. Both
mouse embryonic and human neural precursor cells can be made to prematurely differentiate
towards neuroglial fate with forced expression of Olig2 transcription factor, whereas coexpression
of Olig2 and Nkx2.2 leads to premature oligodendroglial fate specification, compared
to placebo. The quantitative effect of fate switching was marked with embryonic stem cell
differentiation. Forced expression of key transcription factors as illustrated, may be an attractive
method to control stem cell fate modification in in-vitro, and this may successfully be used to
generate rare live human cells (such as Oligodendroglia or other specialized cells) for further
experiments. | en_US |
