Welcome to my report from the 9th Annual ISSCR Meeting in Toronto, 2011. This is part three, covering the events of day three of the conference (Friday); you can read the coverage from day one here and day two here.
Day 3 – Friday 17th June
Starting off the day and the ‘Reprogramming and Fate Conversion’ plenary session, Shinya Yamanaka (Center for IPS Cell Research & Application, Japan), somewhat of a celebrity at the conference for his work to generate the first human iPSCs, talked about his lab’s ongoing work in this field, on the comparison between iPSCs and ESCs, and the use of Glis1 as a reprogramming factor. John Gurdon (from the eponymous Gurdon Institute in Cambridge) presented his work studying the reprogramming of a somatic cell nuclei by nuclear transfer into Xenopus oocytes, a reprogramming event that occurs, unlike iPSC reprogramming, at a 100% efficiency. Eric Kallin stepped in for Thomas Graf (both from Center for Genomic Research, Spain) to talk about the role of Tet2 in the transdifferentiation of B cells to macrophages. From Mount Sinai Hospital in our host city, Andras Nagy described his lab’s work using transposons to reprogram somatic cells towards induced pluripotency, and also unveiled a multi-centre project to comprehensibly map the time course for changes in protein, RNA, and DNA during reprogramming, appropriately named “Project Grandiose” – the results of which are due at next year’s conference. Finally, Rudolf Jaenisch (Whitehead Institute for Biomedical Research) discussed his work investigating the efficiency of reprogramming.
In the ‘Haematopoietic Stem Cells’ concurrent session, host Tannishtha Reya (UCSD) presented work concerning Numb & Mushashi in control of asymmetrical division in CML, and Momoko Yoshimoto (Indiana University School of Medicine) gave a talk entitled ”Multipotent haematopoietic progenitors arise at the extra-embryonic yolk sac prior to hematopoietic stem cell emergence in the mouse embryo’. Next, Trista North (Harvard) talked about the control of HSCs in Zebrafish by reactive oxygen species and HIFα, and Rong Lu (Stanford) described her work using genetic ‘barcodes’ to track single murine HSC differentiation in vivo – multiple short DNA sequences are integrated using lentiviruses into HSCs, and after transplantation, the differentiated progeny are harvested and sequenced for the presence of these ‘barcodes’.
To finish, the other host of the session, Andreas Trumpp from DKFZ in Germany, battled through technical difficulties to give a talk that roughly divided into two parts. Firstly, he discussed the discovery of a particular subset of HSCs which divided extremely slowly (estimated at 5 divisions in a lifetime). This dormant HSC population sheds light onto how leukaemic stem cells evade damage by chemotherapy. Application of IFNα or LPS could ‘wake-up’ dormant HSCs and LSCs, indicating a potential mechanism with which to improve chemotherapy. To finish off his talk, Andreas switched to looking at breast cancer, and whether Metastatis Initiating Cells (MICs) could be identified in tumour cells circulating in the blood (called Circulating Tumour Cells, or CTCs). The key was to find CTCs of a breast cancer stem cell phenotype that had hallmarks of Mesenchymal-to-Endothelial Transition.
Back in the main lecture hall for the ‘Stem Cell Metabolism and Ageing’ plenary, Sean Morrison (University of Michigan Centre for Stem Cell Biology) derscribed his work attempting to characterise the haematopoietic stem cell niche. Irina Conboy (UCBerkley) presented work on the regulation of the Muscle Stem Cells and niche during ageing. Amy Wagers (Harvard) later on in the session gave a talk on a similar topic, including the identification of small molecules involved in muscle repair and the role of calorie intake in muscle damage.
Margaret Goodell from Baylow College of Medicine talked about her lab’s work investigating the role of DNA methylation by Dmnt3a in the regulation of haematopoietic stem cells. A conditional mutant mouse that deletes Dmnt3a in haemtopoietic cells (Mx1-Cre) showed an unexpected phenotype upon serial reconstitution of irradiated recipients; the recovery of the numbers of stem cells increased dramatically with each subsequent graft, with their differentiation capacity decreasing. This indicated that Dmnt3a is involved in the control of self-renewal and differentiation of HSCs. When global DNA methylation was analysed, both hypomethylated and hypermethylation was observed; these differentially methylated regions corresponded to genes upregulated and downregulated in leukemias, respectively. However, gene expression data did not strongly correlated with the DNA methylation patterns, and it was still unclear why, despite a variety of haematological disorders commonly showing mutations in Dmnt3a, these mice didn’t succumb to such diseases.
Read on for my report from final day of the ISSCR meeting here.