Towards generating transplantable hematopoietic stem cells from induced pluripotent stem cells

Dr. Niels-Bjarne R. Woods, Ph.D.
Assistant Professor, Lund Stem Cell Center, Molecular Medicine and Gene Therapy, Lund University, Sweden.
Tuesday, August 5, 2014 - 10:00am
MaRS- TMDT R# 4-204, 4th floor
Invited Speaker Seminar
The ability to generate HSCs from patient derived iPS cells, would enable the generation of an unlimited supply of HLA-matched cells, capable of reconstituting the hematopoietic system of patients with hematological disorders and malignancies. We have recently developed an optimized cell-culture protocol to efficiently generate hematopoietic lineages from human iPS cells, with up to 90% blood (CD45+) cells obtained including generating primitive progenitors with lymphoid and myeloid differentiation ability, and capable of limited short-term hematopoietic reconstitution in immune compromised mice. We have used this system as a model for human hematopoietic development to explore novel factors involved in commitment of precursors of the hematopoietic lineage and in the maturation of HSC-like cells. I will present recent our findings that retinoic acid signaling is a potent effector of hematopoietic lineage commitment with actions a multiple stages during development. We provide evidence that RA is a negative regulator of mesodermal formation and the downstream precursors of the hematopoietic lineage, and that it promotes the exhaustion of definitive hematopoietic progenitors. We further propose that the blood lineage, including precursors thereof, evolved in a RA low environment in the developing embryo. I will also present our work on some signaling mechanisms that we have recently identified having a role in HSC-like cell development.
Dr. Rama Khokha, Professor, Dept. of Medical Biophysics, and Senior Scientist, Ontario Cancer Institute/Princess Margaret Cancer Centre
OCI Special Seminar
Ontario Cancer Institute/Princess Margaret Cancer Centre