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 aging. We have decided to focus on mechanisms that regulate stem cell self-renewal, stem cell aging, and organogenesis from stem cells. By studying these mechanisms in parallel using stem cells from two different tissues we will assess the extent to which different types of stem cells employ similar or different mechanisms to regulate these critical functions.
Representative Publications:
- Bixby, S., G.M.. Kruger, J.T. Mosher, N. Joseph, and S.J. Morrison. 2002. Cell-intrinsic differences between neural stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron 35:643-656.
- Kruger, G.M., J. Mosher, S. Bixby, N. Joseph, T. Iwashita, and S.J. Morrison. 2002. Neural crest stem cells persist in the adult gut but undergo perinatal changes in self-renewal potential, neuronal subtype potential, and responsiveness to lineage determination factors. Neuron 35:657-669.
- Kruger, G.M. and S.J. Morrison. 2002 Brain repair by endogenous progenitors. Cell 110:399-402.
- Iwashita, T., G.M. Kruger, R. Pardal, M.J. Kiel, and S.J. Morrison. 2003. Hirschsprung disease is linked to defects in neural crest stem cell function. Science 301:972-976.
- Alvarez-Dolado, M., R. Pardal, J.M. Garcia-Verdugo, J.R. Fike, H.O. Lee, K. Pfeffer, C. Lois, S.J. Morrison and A. Alvarez-Buylla. 2003. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968-973.
- Molofsky, A.V., R. Pardal, T. Iwashita, I-K. Park, M.F. Clarke, and S.J. Morrison. 2003. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962-967.
- Al-Hajj, M., M.S. Wicha, A. Benito-Hernadez, S.J. Morrison, and M.F. Clarke. 2003. Prospective identification of tumorigenic breast cancer cells. PNAS USA 100:3983-3988
- Pardal, R., M.F. Clarke, and S. J. Morrison. 2003. Applying the principles of stem cell biology to cancer. Nature Reviews Cancer 3:895-902.
- Kiel, M.J., O.H. Yilmaz, T. Iwashita, O.H. Yilmaz, C. Terhorst, and S.J. Morrison. 2005. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121: 1109-1121
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