| 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 initiation of neuro or glial cell fate
specification phase in rodents and humans. The
aim of the study was 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 invivo
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 cotranscription
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 co-expression 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 specialised cells) for further
experiments. | en_US |
