Research Project Outline
Generation of self-renewing human hematopoietic stem cells (HSCs) from ES cells or iPS cells is a challenging project. Our proposal aims to solve this problem. To this end, we fi rst un-derstand the epigenetic status, particularly the histone modi-fi cation profi les of adult HSCs. We also characterize the role of polycomb genes, important regulators of histone modifi ca-tions, in the maintenance of HSCs and reprogramming of hematopoietic cells to pluripotency. These approaches should provide critical epigenetic regulatory machinery that deter-mines adult HSCs. Finally, we identify the epigenetic programs essential for generation of adult HSCs from iPS-derived em-bryonic hematopoietic progenitors. By applying all these results to HSC induction from iPS cells, we hope to provide a road map for iPS cell-based regenerative medicine in the lympho-hematopoietic field.