Peter van Galen focuses on understanding the determinants that maintain the stem cell state. Using human hematopoietic stem
cells (HSCs) as a model, processes that govern self-renewal and tissue regeneration were investigated. Specifically, a role
for microRNAs in balancing the human HSC quiescence/proliferation equilibrium was uncovered. By attenuating PI3K/AKT signaling,
miR-126 restrains HSC proliferation. Second, it was shown that ID proteins restrain expression of differentiation-associated
genes in HSCs (lineage priming), thereby enhancing self-renewal of HSCs. Exploiting the link between lineage priming and the
stem cell state can be used to successfully expand human HSCs in vivo. As well, a new role for stress signaling in the maintenance
of HSC pool integrity was uncovered. Through differential activation of the Unfolded Protein Response pathway in HSCs compared
to progenitors, damaged HSCs are purged from the blood system. This process is thought to limit damage accumulation in the
stem cell pool and enable tissue regeneration throughout life. Overall, mechanisms are uncovered that balance human HSC quiescence/proliferation,
self-renewal/differentiation and apoptosis/survival.
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