November was a big month for science in Canada.
Our new prime minister, Justin Trudeau, sent a clear message that science will be a priority for his administration by naming Dr. Kirsty Duncan Minister of Science, and Navdeep Bains Minister of Innovation, Science and Economic Development.
Following closely on these exciting political developments, a landmark study on blood stem cells came out of Dr. John Dick’s lab at the Princess Margaret Cancer Centre in Toronto. The study, published November 5 in the journal Science, will fundamentally reshape our understanding of how blood is made.
Dr. Dick’s work follows in the distinguished tradition of Canadian scientists Dr. James Till and Dr. Ernest McCulloch who, in 1961, were the first to identify transplantable blood stem cells. Based on their work, the concept of a cellular hierarchy in blood development emerged.
In a news release on this breakthrough study, Dr. Dick explains that blood stem cells support the constant regeneration of our blood, and regulate the daily turnover of more than 300 billion blood cells.
The standard model – the dominant theory of blood development – has primarily informed our understanding of how the blood system continuously regenerates itself. According to the standard model, self-renewing blood stem cells are at the apex of the blood cell lineage. Through a gradual and step-wise process, blood stem cells give rise to a diverse set of fully differentiated blood cells.
However, the Dick lab began questioning the standard model based on evidence that blood cells didn’t always follow this highly stereotyped developmental pathway. Their approach was to carefully analyze lineage forming potential, in individual blood stem cells, using newly developed and more sensitive assays (tests).
They analyzed approximately 3,000 human blood stem cells obtained from fetuses and adults. First, they determined that the makeup of our blood stem cells changes as we progress to adulthood. Next, they provided evidence that in adults, blood stem cells can be separated into two distinct tiers of immature stem cells and mature blood cells. Thus doing away with the concept that blood cells arise from a series of linked developmental steps.
This work has many important implications for patients. First, it will shed new light on blood disorders like anemia and leukemia, where the balance of blood cell production is abnormal. From a regenerative medicine standpoint, a better understanding of the blood development process will help us fine tune protocols for deriving mature blood cells from induced pluripotent stem cells (iPSCs). Dr. Dick has collaborated with Dr. Gordon Keller, Director of UHN’s McEwen Centre for Regenerative Medicine, to develop better protocols for the derivation of red blood cells and platelets from iPSCs – a necessity. Currently, human donors are the only available source of platelets and red blood cells that are required for blood transfusions.
The recent study out of Dr. Dick’s lab is the product of an entire career focused on blood stem cell biology.
Sustained, long-term work on complex biological questions is only possible with reliable sources of funding. There is a sense of hope, in Canada, that our changed political landscape, and a renewed emphasis on science, will lead to better funding. More money will ensure that Canada continues to lead the way in the study of regenerative medicine and stem cell biology.
Notta F, Zandi S, Takayama N, Dobson S, Gan OI, Wilson G, Kaufman KB, McLeod J, Laurenti E, Dunant CF, McPherson JD, Stein LD, Dror Y, Dick JE. (2015) Distinct routes of lineage development reshape the human blood hierarchy across ontongeny. Science ahead of print.
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