Niche oncogenesis

Published on March 5, 2014   35 min
This is David Scadden. I'm hematologist-oncologist at Mass General Hospital, co-direct the Harvard Stem Cell Institute, and co-chair of the Department of Stem Cell and Regenerative Biology at Harvard University. I'll be talking today about niche oncogenesis, the role of the hematopoietic stem cell niche in particular, and the development of malignancy.
The stem cell niche is a concept first proposed by Ray Schofield back in 1978 when he was looking at blood stem cells. At the time, the method by which cells were analyzed was called a colony-forming unit of the spleen-- a so-called CFU-S. And he recognized that stem cells that he had been able to isolate from the spleen in these colonies seemed to behave less robustly than stem cells derived from the bone marrow. And he proposed what now seems to be an entirely obvious concept, that where a stem cell resides was in some ways playing a critical role for its function-- that the niche was the basis for stem cells having regulated self-renewal and differentiation. It was a competing hypothesis at the time, which was that stem cells had their own intrinsic engineering and were capable of going in the direction that they knew best. And it was Ray Schofield who proposed that there was this imposition of information from the tissue in which the stem cell resided. It was a concept initially, and one that really did not have much in the way of experimental definition until some years later and mostly in invertebrates.