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Singapore General Hospital researchers, Dr. Zhi-Ching Xiao and his team, makes breakthrough in stem cell research.

One of the major hopes of stem cell research is to cure diseases of the central nervous system (CNS) such as Alzheimers, Parkinsons and Multiple Sclerosis. Three types of stem cells could be used for these therapeutic applications; adult stem cells from cord blood or bone marrow, embryonic stem cells or neural stem cells. Each of these cell types has advantages and disadvantages and work is actively going on all three cell types. What is clear is that our understanding of how to turn stem cells into effective therapies is at best rudimentary. We must understand in more detail how to control the cell fate of stem cells by gaining more insight into the cell and developmental biology programmes of stem cells.

Control of cell fate is a very active area of stem cell research. One such example would be controlling the cell fate of neural stem cells or Oligdendrocyte persursor cell's (OPC's) into Oligodendrocyte's (OL's), cells that have the ability of myelinate axons (1). The well known ligands of the Notch receptor, Jagged and Delta, are implicated in controlling the differentiation of precursors into OL's. Studies by a number of groups have suggested that Notch signaling inhibits the differentiation of OL's(2,3). There is also evidence that downregulation of Notch increases myelination. On the other hand Notch plays an instructive role required for the generation of OPCs. Delta ligand KO mice and Zebrafish Delta mutants are defective in OPC generation (4,5).

Xiao and colleagues, have identified the cell surface contact molecule contactin/F3 as a novel ligand for the Notch receptor (6). The contactin/F3-Notch interaction induces differentiation of OL-93 cells into OLs (6). Dominant negative inhibitors of Notch signaling inhibited the effect of contactin/F3 suggesting that the classical Notch pathway is involved. The novel interaction of contactin/F3 with the Notch receptor opens new avenues to understand how OLs interact with neurons as well as therapeutic approaches to demyelination diseases. In a follow-up paper Xiao and colleagues have shown that neural stem cell differentiation is also susceptible to contactin/F3 control (7).

References

1. Prog. Neurobiol. 67(2002), 451-467.
2. Neuron: 21(1998), 63-75.
3. J. Neurosci. Res.:67(2002), 309-320.
4. Development: 130 (2003), 3747-3755.
5. Development: 130 (2003), 1391-1402.
6. Cell:115 (2003), 163-175.
7. J. Biol. Chem: 279, (2004) 25858-25865.