Thirty Years of Stem Cell Randomness (As Discussed on the Bayblab Pubcast)

As discussed previously on the bayblab podcast (Episode 6 part 3) it was Canadian research pioneers Till, McCulloch, and Siminovitch who first discovered hematopoietic stem cells and, amongst other things, described their perplexing stochastic behaviour. Through elegant experiments involving serial passage of bone marrow derived "spleen colony-forming" HSCs in live mice (they didn't have the funding to use the high-tech and expensive system known as "cell culture"), they nicely demonstrated that the fate of individual daughter cells resulting from stem cell mitosis is not predictable or deterministic, but rather stem cell division is a probabilistic event when large populations are observed. A short paper, well-written and definitely worth the read (A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. PNAS, 1964). I also posted the figures below just because they're so 60s cool. I don't know exactly what people in the field thought at the time the paper was published, but my interpretation is that biology hasn't really been equipped to explain this type of behaviour, until just recently technical advances have allowed us to look at gene expression and other cell behaviours in real time at the single-cell level.

Thirty years later, these types of approaches are reveleaing the fascinating dynamics of cell behaviour. Case in point: today's lecture at the OHRI by Eric Jervis, an engineer from the University of Waterloo, who has built custom technology to microscopically observe and track the behaviour of large numbers of individual cultured cells. The cells are captured on digital video and lingeages tracked over multiple rounds of cell division. Lineages were visualized on a typical pedigree type diagram. Anyway, the videos were just too awesome to convey in words. Not many of them can be found in published literature, but this cool one from a 2006 PNAS publication (click on the image below to view the video) captures individual hematopoietic stem cells in the act, giving rise to colonies of highly variable cell number and proliferative rates upon explant into culture. Strikingly similar findings to those of McCulloch, Till and Siminovitch thirty years ago, now live and in digital format...