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?