Our UHN programs and services are among the most advanced in the world. We have grouped our physicians, staff, services and resources into 10 medical programs to meet the needs of our patients and help us make the most of our resources.
University Health Network is a health care and medical research organization in Toronto, Ontario, Canada. The scope of research and complexity of cases at UHN has made us a national and international source for discovery, education and patient care.
Our 10 medical programs are spread across eight hospital sites – Princess Margaret, Toronto General, Toronto Rehab’s five sites, Toronto Western – as well as our education programs through the Michener Institute of Education at UHN. Learn more about the services, programs and amenities offered at each location.
Maps & Directions
Find out how to get to and around our nine locations — floor plans, parking, public transit, accessibility services, and shuttle information.
Ways You Can Help
Being touched by illness affects us in different ways. Many people want to give back to the community and help others. At UHN, we welcome your contribution and offer different ways you can help so you can find one that suits you.
The Newsroom is the source for media looking for information about UHN or trying to connect with one of our experts for an interview. It’s also the place to find UHN media policies and catch up on our news stories, videos, media releases, podcasts and more.
Toronto (Nov. 25, 2020) – Princess Margaret scientists have revealed how stem cells are able to generate new blood cells throughout our life by looking at vast, uncharted regions of our genetic material that hold important clues to subtle biological changes in these cells.
The finding, obtained from studying normal blood, can be used to enhance methods for stem cell transplantation, and may also shed light into processes that occur in cancer cells that allow them to survive chemotherapy and relapse into cancer growth many years after treatment.
Using state-of-the-art sequencing technology to perform genome-wide profiling of the epigenetic landscape of human stem cells, the research revealed important information about how genes are regulated through the three-dimensional folding of chromatin.
Chromatin is composed of DNA and proteins, the latter which package DNA into compact structures, and is found in the nucleus of cells. Changes in chromatin structure are linked to DNA replication, repair and gene expression (turning genes on or off).
The research by Princess Margaret Cancer Centre Senior Scientists Drs. Mathieu Lupien and John Dick is published in
Cell Stem Cell, Nov. 25.
"We don't have a comprehensive view of what makes a stem cell function in a specific way or what makes it tick," says Dr. Dick, who is also a Professor in the Department of Molecular Genetics, University of Toronto.
"Stem cells are normally dormant but they need to occasionally become activated to keep the blood system going. Understanding this transition into activation is key to be able to harness the power of stem cells for therapy, but also to understand how malignant cells change this balance.
"Stem cells are powerful, potent and rare. But it's a knife's edge as to whether they get activated to replenish new blood cells on demand, or go rogue to divide rapidly and develop mutations, or lie dormant quietly, in a pristine state."
Understanding what turns that knife's edge into these various stem cell states has perplexed scientists for decades. Now, with this research, we have a better understanding of what defines a stem cell and makes it function in a particular way.
"We are exploring uncharted territory," says Dr. Lupien, who is also an Associate Professor in the Department of Medical Biophysics, University of Toronto. "We had to look into the origami of the genome of cells to understand why some can self-renew throughout our life while others lose that ability. We had to look beyond what genetics alone can tell us."
In this research, scientists focused on the often overlooked noncoding regions of the genome: vast stretches of DNA that are free of genes (i.e. that do not code for proteins), but nonetheless harbour important regulatory elements that determine if genes are turned on or off.
Hidden amongst this noncoding DNA – which comprise about 98 per cent of the genome – are crucial elements that not only control the activity of thousands of genes, but also play a role in many diseases.
The researchers examined two distinct human hematopoietic stem cells or immature cells that go through several steps in order to develop into different types of blood cells, such as white or red blood cells, or platelets.
They looked at long-term hematopoietic stem cells (HSCs) and short-term HSCs found in the bone marrow of humans. The researchers wanted to map out the cellular machinery involved in the "dormancy" state of long-term cells, with their continuous self-renewing ability, as compared to the more primed, activated and "ready-to-go" short-term cells which can transition quickly into various blood cells.
The researchers found differences in the three-dimensional chromatin structures between the two stem cell types, which is significant since the ways in which chromatin is arranged or folded and looped impacts how genes and other parts of our genome are expressed and regulated.
Using state-of-the-art 3D mapping techniques, the scientists were able to analyze and link the long-term stem cell types with the activity of the chromatin folding protein CTCF and its ability to regulate the expression of 300 genes to control long-term, self-renewal.
"Until now, we have not had a comprehensive view of what makes a stem cell function in a particular way," says Dr. Dick, adding that the 300 genes represent what scientists now think is the "essence" of a long-term stem cell.
He adds that long-term dormant cells are a "protection" against malignancy, because they can survive for long periods and evade treatment, potentially causing relapse many years later.
However, a short-term stem cell that is poised to become active, dividing and reproducing more quickly than a long-term one, can gather up many more mutations, and sometimes these can progress to blood cancers, he adds.
"This research gives us insight into aspects of how cancer starts and how some cancer cells can retain stem-cell like properties that allow them to survive long-term," says Dr. Dick.
He adds that a deeper understanding of stem cells can also help with stem cells transplants for the treatment of blood cancers in the future, by potentially stimulating and growing these cells
ex vivo (out of the body) for improved transplantation.
The research was supported by The Princess Margaret Cancer Foundation, Ontario Institute for Cancer Research, Canadian Institutes for Health Research (CIHR), Medicine by Design, University of Toronto, Canadian Cancer Society Research Institute, and the Terry Fox Research Institute.
Dr. John Dick served on the SAB at Trillium Therapeutics, and has ownership interest (including patents) in Trillium Therapeutics. He also reports receiving a commercial research grant from Celgene.
Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital, Toronto Rehabilitation Institute and the Michener Institute for Education at UHN. All are research hospitals affiliated with the University of Toronto. For more information:
Phone: 416 340 4636