Welcome to my report from the 9th Annual ISSCR Meeting in Toronto, 2011. This is part two, covering the events of day two (Thursday) of the conference, you can see part one here.
Day 2 – Thursday 16th June
Arriving late at the first plenary of the day, “Tissue Stem Cell Origins”, I managed to catch Michael Rudnicki (Ottawa Health Research Institute) talk about his work on role of Carm1 in muscle stem cell function. Next, in a talk entitled ‘Endothelial Origins of Haematopoietic Precursors’, Elaine Dzierzak of the Erasmus Stem Cell Institute in the Netherlands present her lab’s work identifying the emergence of haematopoietic progenitors from the aortic endothelium during early mouse development. The visualisation of these ‘haematopoietic clusters’ has been made possible by making the embryo transparent and using multi-colour confocal imaging, giving a 3D map of vasculature and the establishment of early haematopoiesis, starting at E9.5 and peaking a day later. Finishing off the plenary session was Hans Clevers from Hubrecht Institute, and his lab’s fascinating work identifying intestinal stem cells in vivo, involving some ingenius imaging work, and their role in cancer, involving self-replicating and self-organising ‘miniguts’ (see the recent Nature paper from his lab for work on Wnt signalling in regulating instestinal crypt stem cells).
The concurrent sessions of the conference started today (five parallel sessions each day), and so I took the opportunity to dart between seminar rooms to see a variety of talks. First up, in the ‘Stem Cells & Tissue Engineering’ session, was Peter Zandstra (University of Toronto), speaking about his group’s work with the integration of reprogramming, pluripotency maintenance, and differentiation into a suspension-culture bioreactor, in particular for differentiation towards pancreatic and cardiac lineages. I found it fascinating, and timely – if regenerative medicine is ever going to be available to large numbers of people, it will have to be at an industrial scale, and Peter’s talk outlined some of the first steps towards these goals.
I then went to the ‘Human iPSCs and ESCs’ session. Amy Wong (Hospital for Sick Children, Toronto) talked about generating lung airway epithelium from Cystic Fibrosis patient-derived iPSCs in liquid-air interfaces, which would be useful for modelling the disease. Shannon Buckley (NYU School of Medicine) gave a talk on Ubiquitination, an often forgotten mechanism of regulation of ESC self-renewal and differentiation. Natalia Ivanova (Yale) gave an overview of the interactions between Nanog, Sox2, and Oct4 as a regulatory module in hESCs, and Duanqing Pei (GIBH, China) discussed his lab’s methods to increase the efficiency of inducing pluripotency, something that, again, will be critical if ‘personalised medicine’ using patient derived iPSCs is ever to become a realistic prospect for the majority.
The final plenary session of the day was concerned with the biology of Cancer Stem Cells. To start off, Thea Tlsty, from University of California in San Francisco, described the discovery of a new population of cells derived from triple negative breast cancers. They have the ability to form mammospheres, which have all the normal breast tissue structures and can produce milk under hormonal stimulation, both in vitro and upon xenograft in vivo. However, the real intrigue begins as she described how these cells will also produce cells of all three germ-layer lineages when implanted in various locations, and can also form teratomas, properties normally reserved to desribe human pluripotent stem cells. These cells, though mortal, can even be cultured as hESCs, and bear their normal pluripotency markers of Nanog, Sox2, and Oct4. Thea concedes that more investigation is needed, and has cautiously named these cells ePPSCs – endogenous, provisionally pluripotent, somatic cells (perhaps to avoid any wrath from Irv Weissman!?)
Pier Paolo Di Fiore (University of Milan) talked about the role of Numb regulation of Notch signalling in breast cancer stem cells, using ex vivo self organising organs called ‘mammospheres’, echoing Hans Clever’s talk from earlier in the day. Stanford’s Michael Clarke presented his group’s work in the haematopoietic system, specifically looking at Bmi1 and cancer stem cell self-renewal.
In the Ernest McCulloch Memorial Lecture, John Dick from the University Health Network in Toronto, reflected on the necessity of functional assays to describe the differentiation capacity of haematopoietic stem and progenitor cells, thus underlining the importance of McCulloch’s contributions to the field. He then went on to talk about the concept of ‘clonal evolution’ in human leukaemias, the phenomenon where the major disease causing leukemic population is in fact one of many competing clones. When treatment kills off the major clone sending the patient into remission, previously hidden clones are now free to proliferate and cause a relapse. John stated that consolidating this model with that of the ‘cancer stem cell’ is the current challenge, and finished with describing some recent papers that start to bridge the gap between genetic and functional diversity of cell populations in a variety of leukaemias.
The second day of the ISSCR meeting ended with a reception, whilst half of the poster presenters stood faithfully by their offering of from the 1,500 posters. Later that evening, 1,000 people (allegedly) crammed into a club in downtown Toronto for a “social evening”, which I’m sure resulted in many sore heads the next morning! (mine included…). Read on for the report from day three here.