Godot

I've been wondering: is it yet known at what point pluripotent stem cells lose their differentiating ability?
In a related query, what acts upon the cell to cause this change?

tribalbeeyatch

I think that you've just asked the current $64,000 questions in stem cell biology.

Godot

Fair enough. I guess what I was getting at was if it is yet to be known, have any hypotheses been advanced?

tribalbeeyatch

I do a little bit of work on neural stem cells, and I would say that we have identified certain growth factors that maintain multipotency and others that encourage differentiation. We also know some of the intracellular signaling events that go along with differentiation, but I don't think it's really known what sorts of mechanistic shifts this signaling provokes. I mean, we know that structural proteins are expressed and transcription factors/enhancers are upregulated, for example, but we haven't really identified the key process(es) that makes differentiation a dead-end street.

Wounded King

Godot,

You should look into the niche hypothesis. There is a lot of work on the environmental factors which allow certain populations of cells to maintain pluripotency while their sibling daughter cells move on to a differentiated fate.

Lin H.
The stem-cell niche theory: lessons from flies.
Nat Rev Genet. 2002 Dec;3(12):931-40.

TTFN,

Wounded

Godot

Thanks for that. I'll check it out.

Wounded King

The extent to which differentiation is a dead end street is debatable. There is much work going on at the moment into transdifferentiation from one tissue type to another.

See

Horb ME, Shen CN, Tosh D, Slack JM. Experimental conversion of liver to pancreas.
Curr Biol. 2003 Jan 21;13(2):105-15.

From the lab of Jonathan Slack, the man who brought you headless frog embryos.

tribalbeeyatch

It is certainly debatable (what isn't?), but there really doesn't seem to be much a faction arguing that differentiation is irreversible/inalterable given the right sorts of therapeutic interventions. It isn't heretical in the slightest to suggest that cell fate determination might not be indelible. I hope that my "dead-end street" comment wasn't taken in that vein; I meant it more as a metaphor for the process of differentiation rather than the future of that avenue of research.