Stem cells
are self-renewing multipotent progenitors that give rise
to all of the other cells in particular tissues. For
example, hematopoietic stem cells (HSCs) are the rare
cells in bone marrow that give rise to all blood and
immune system cells. Neural crest stem cells give rise to
a number of different tissues including the peripheral
nervous system. Given their seminal roles in development
and regeneration, stem cells define the nexus of
important questions in both developmental biology and
clinical applications. We study stem cell biology using
hematopoiesis and neural development as model systems.
The next challenge in stem cell biology will be to
integrate what we know about stem cells in different
tissues in order to understand common mechanisms of
regulation and distinctions that permit
tissue-appropriate development. Our work on stem cell
regulation encompasses both molecular and cellular
questions, from the role of transcription factors in cell
fate determination to changes in the properties of stem
cells during ontogeny.
Conserved genetic programs may regulate stem cell
self-renewal in the hematopoietic and nervous systems. We
study the regulation of self-renewal in both HSCs and
neural crest stem cells (NCSCs). We have complementary
tools available in the two systems given our ability to
isolate HSCs with successive reductions in self-renewal
potential in vivo and our ability to purify NCSCs by
flow-cytometry and study their self-renewal in vitro. We
have previously shown that telomerase and Ikaros may play
roles in the self-renewal and differentiation of HSCs. To
the extent that changes in telomerase and Ikaros
expression have been implicated in tumorigenesis, genetic
programs that regulate the self-renewal of stem cells may
be inappropriately activated in cancer cells.
A distinction between the hematopoietic and nervous
systems is the regional specialization that develops in
the nervous system. This is at least partially driven by
regulation at the level of stem cells and suggests
aspects of regulation that do not exist in the
hematopoietic system. Based on our recent finding that
NCSCs persist into late gestation in peripheral nerves we
will study whether similar or different types of stem
cells persist in other regions of the developing nervous
system. To what extent is neural diversity driven by the
diversification of stem cells and how does this affect
plasticity?
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