Stem Cells: Doing Some Heavy Lifting at ISSCR 2011
2011; Elsevier BV; Volume: 9; Issue: 4 Linguagem: Inglês
10.1016/j.stem.2011.09.009
ISSN1934-5909
Autores Tópico(s)Planarian Biology and Electrostimulation
ResumoThis year's International Society for Stem Cell Research (ISSCR) annual meeting was an opportunity for attendees to be inspired by early successes, to grapple with the challenges of applying emerging technologies, and to contemplate moving with increasing but cautious optimism toward the clinic. This year's International Society for Stem Cell Research (ISSCR) annual meeting was an opportunity for attendees to be inspired by early successes, to grapple with the challenges of applying emerging technologies, and to contemplate moving with increasing but cautious optimism toward the clinic. The 2011 ISSCR Annual Meeting was held in Toronto, Canada, under the auspices of the Annual Meeting Program Committee chaired by Haifan Lin (Yale University School of Medicine). This year's gathering had an upbeat and inspirational feel that was fueled by a presidential session that looked back on early successes of the society, recounted recent scientific developments, and described fledgling steps toward the clinic for new stem cell treatments. Throughout the meeting, one could not help but feel that palpable progress was being made and that, in small but ever-increasing increments, the promise of stem cell research was being realized. The almost motivational nature of the ISSCR meeting was further “enhanced” by the fitness professionals and techno beats emanating from the neighboring body building expo that mingled with the stem cell research community in the Toronto Convention Center. Altogether, one was left with the impression that the field of stem cell research was rapidly maturing and finally ready to take on some heavy lifting.Shinya Yamanaka, M.D., Ph.D., and Kazutoshi Takahashi, Ph.D., received the ISSCR McEwen Centre Award for Innovation. Left to right: Rob McEwen, Fred H. Gage, Cheryl McEwen, Kazutoshi Takahashi, and Shinya Yamanaka.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The meeting began in earnest with the Welcome and State of the Society Address by the outgoing president, Elaine Fuchs. In addition to documenting the growth and strength of the society, she described significant new initiatives that would soon be launched, including an important effort in developing educational materials. Her address culminated in the presentation of the ISSCR's public service award to Robert Klein, outgoing Chairman of the California Institute of Regenerative Medicine's (CIRM's) Independent Oversight Committee. Klein received the award in recognition of his instrumental role in the initiation and passage of Proposition 71, the voter referendum that established CIRM and led to 3 billion dollars of support for stem cell research in California. This was indeed a very timely award, because this year in particular, it was clear that the positive effects of CIRM support were being felt in earnest. Funding directly from the state of California was cited as instrumental for the success of many projects described by speakers at this year's meeting. Following the presentation to Klein, Fuchs charged the next two scientific speakers in her session to look back and provide a historical perspective on the topics they discussed. This charge was first taken up by Janet Rossant (Hospital for Sick Children, Canada), who in her talk provided a wonderful, brief history of mammalian stem cell research. She first described Till and McCulloch's work on the blood-forming stem cell and then recounted the discovery of pluripotent teratocarcinomas. She proceeded to explain how the discovery of teratocarcinomas led to the derivation of embryonal carcinoma cells and finally the isolation of the first embryonic stem cell (ESC) lines. She then went on to share some recent results from her group that potentially explain why ESCs do not ordinarily contribute to the primitive endoderm after injection into the blastocyst. In particular, it was fascinating to hear about the prominent role played by Canadian scientists in the advancement of the stem cell field. Rossant passed the podium on to a former president of the society, George Daley (Children's Hospital Boston, USA). Following her lead, Daley provided a similarly exciting description of the origins of the field of nuclear reprogramming. His remarks were informative, humorous, and enjoyable. Entertainingly, he ranged from the description of early cloning experiments carried out by John Gurdon and colleagues to the first successful mammalian cloning experiments, and then culminated with the development of induced pluripotency by Katzutoshi Takahashi and Shinya Yamanaka. Daley then went on to highlight the many opportunities that induced pluripotent stem cell (iPSC) reprogramming now offers in the area of in vitro disease modeling. A major theme of the meeting—that of how to implement stem-cell-based therapeutic strategies in humans—was set forth in the Keynote Address by Robert Langer (Massachusetts Institute of Technology, USA), who discussed the critical role of bioengineered materials. The successful delivery of compounds, nucleic acids, or even cell products in a controlled manner requires high-throughput screens to identify variants of existing scaffolds or combinations of materials that optimize their physical properties while minimizing immunogenicity. To this end, a recent study showed that specific lipid derivatives, when combined, could mediate high-level siRNA-driven knockdown of gene expression even if each lipid was ineffective alone (Whitehead et al., 2011Whitehead K.A. Sahay G. Li G.Z. Love K.T. Alabi C.A. Ma M. Zurenko C. Querbes W. Langer R.S. Anderson D.G. Mol. Ther. 2011; 19: 1688-1694Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar). The push to move novel therapies into the clinic for profit comes with the risk of premature testing in humans and even fraudulent claims that an approach is “proven effective.” The marketing of stem cell therapy before safety and efficacy are demonstrated is an ongoing issue, which was highlighted by the ISSCR in 2010 and again this year by Irving Weissman (Stanford University School of Medicine, USA). Weissman emphasized the importance of clear nomenclature in establishing an ironclad definition of a particular adult stem cell. Single-cell clonality in conjunction with transplantation, as employed in the hematopoietic stem cell (HSC) field, he argued, is absolutely required for a rigorous definition of a stem cell. Weissman laid out a set of criteria that should be in place before a stem cell treatment is marketed or adopted as a standard of care: (1) preclinical proof of principle, (2) verification of data in independent laboratories, (3) involvement of a medical ethics committee such as a hospital institutional review board, to protect the rights of human subjects, and (4) approval by an official regulatory body (e.g., by the Food and Drug Administration). The 2011 Outstanding Young Investigator Award was presented to Robert Blelloch (University of California, San Francisco, USA) who screened for microRNAs (miRNAs) that influence self-renewal and differentiation. His laboratory identified ESC-cycle regulating miRNAs (ESCCs) as critical self-renewal factors for mouse ESCs (Melton et al., 2010Melton C. Judson R.L. Blelloch R. Nature. 2010; 463: 621-626Crossref PubMed Scopus (530) Google Scholar). More recently, he tested the concerted effects of opposing miRNA families (ESCCs and let-7 miRNAs) on reprogramming in human iPSCs by influencing pathways related to the mesenchymal to epithelial transition (MET). His unique approach strongly argues for the power of probing reprogramming and other complex phenotypes using a miRNA-based screening strategy. Ruth Lehmann (New York University School of Medicine, USA) discussed how repression is a conserved theme in the restriction of germ cell fate. The Lehmann laboratory has found that maintenance of a germ cell state not only requires suppression of unwanted host gene expression but also specifically that of foreign DNA such as transposable elements. This is accomplished in the germline by piwi-interacting (pi)RNAs, which colocalize with H3K9trimethyl marks at piRNA loci (Rangan et al., 2011Rangan P. Malone C.D. Navarro C. Newbold S.P. Hayes P.S. Sachidanandam R. Hannon G.J. Lehmann R. Curr. Biol. 2011; 21: 1373-1379Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). Azim Surani (University of Cambridge, UK) recounted the remarkable epigenetic odyssey of germline stem cells in mice, which experience at least two distinct rounds of reprogramming in normal development (the first just after fertilization and the second at embryonic day 7.25). He also discussed a parallel model of reprogramming, that of reversion of epiblast stem cells to an ESC-like state (Hayashi and Surani, 2009Hayashi K. Surani M.A. Cell Stem Cell. 2009; 4: 493-498Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). An analogous reprogramming model came from Hans Schöler (Max Planck Institute for Molecular Biomedicine, Germany), who discussed reprogramming of postnatal somatic and germ cells, in addition to epiblast stem cells, and the utility of cell culture to lock the epigenetic state of the cell (Han et al., 2011Han D.W. Greber B. Wu G. Tapia N. Araúzo-Bravo M.J. Ko K. Bernemann C. Stehling M. Schöler H.R. Nat. Cell Biol. 2011; 13: 66-71Crossref PubMed Scopus (99) Google Scholar). From the hematopoietic system to the germ cell lineage, it is becoming apparent that endothelial cells can orchestrate a plethora of functions from stem cell specification to maintenance to differentiation. Owen Tamplin (Zon laboratory, Children's Hospital Boston, USA) presented data on the birth of the HSC during zebrafish development. As in the mouse, a subset of HSCs emerges in intimate association with the vasculature before migrating to the caudal hematopoietic tissue. This process appears to depend on lipid signaling and could be blocked by interfering with the sphingosine-1-phosphate receptor pathway in HSCs. Elaine Dzierzak (Erasmus Medical Center, Netherlands) reviewed disparate sites of developmental hematopoiesis, including development of first HSCs from the aorta-gonad-mesonephros (AGM), visualized with high-resolution fluorescence microscopy and with authenticity proven by transplant (Yokomizo et al., 2011Yokomizo T. Ng C.E. Osato M. Dzierzak E. Blood. 2011; 117: 6132-6134Crossref PubMed Scopus (36) Google Scholar). Interestingly, CD41 was present on both AGM and yolk sac HSCs, but not in the HSCs that form later in development (Robin et al., 2011Robin C. Ottersbach K. Boisset J.C. Oziemlak A. Dzierzak E. Blood. 2011; 117: 5088-5091Crossref PubMed Scopus (51) Google Scholar). Sean Morrison (University of Michigan, USA; recently moved to University of Texas Southwestern Medical Center, USA) reviewed the complexity of the niche in adults, comprising a multicellular environment with potentially overlapping contributions from different cell types. A good example is stem cell factor (SCF), which has been suggested to originate from endothelial, osteoblastic, mesenchymal, and/or uncharacterized stromal cells in the bone marrow. His major conclusion is that HSCs reside in a perivascular niche in which endothelial cells and perivascular stromal cells secrete SCF for HSC maintenance. His work is the first to use genetic approaches to functionally identify the cellular sources of a key niche factor that promote stem cell maintenance in the hematopoietic system. Similarly, Ronald D. McKay (Lieber Institute for Brain Development, USA) raised the question of whether neural recovery after injury could be induced therapeutically by reactivating or enhancing endogenous repair mechanisms from within the niche. Margaret Goodell's laboratory (Baylor College of Medicine, USA) has probed the epigenetic regulation of HSCs. Her experiments using serial transplantation of HSCs in mice indicate that loss of de novo DNA methylation (via methyltransferase gene deletion) in HSCs results in impairment of differentiation, apparently related to hypomethylation at specific differentially methylated regions (DMRs) including some previously implicated in tumorigenesis. Shosei Yoshida (National Institute for Basic Biology, Japan) reviewed recent data challenging the dogma that syncytial spermatogonia in mice are irreversibly committed to differentiation. An evolving view is that the stem cell compartment in the testis is more dynamic and spermatogonia may revert or dedifferentiate to a stem cell state. Time-lapse video has revealed that undifferentiated spermatogonia migrate during differentiation away from vascular zones, for which the underlying reasons have yet to be unraveled. Emi Nishimura (Tokyo Medical and Dental University, Japan) discussed the concept that tissue stem cells can themselves create the niche for other adjacent stem cell types. This fascinating observation is exemplified in the skin, where collagen XVII expression by hair follicle stem cells is required for maintenance of adjacent melanocyte stem cells by providing TGFβ signaling (Tanimura et al., 2011Tanimura S. Tadokoro Y. Inomata K. Binh N.T. Nishie W. Yamazaki S. Nakauchi H. Tanaka Y. McMillan J.R. Sawamura D. et al.Cell Stem Cell. 2011; 8: 177-187Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar). As relayed in a fascinating talk, Scott Williams (Fuchs laboratory, Rockefeller University, USA) studied regulation of the switch between symmetric and asymmetric cell divisions during construction of mammalian skin. Their elegant studies have employed lentiviral shRNA delivered in utero and have found that disruption of asymmetric cell division genes caused functional defects in skin differentiation, leading to hyperpermeability and thinning. These phenotypes were attributable to aberrant loss of Notch signaling during differentiation (Williams et al., 2011Williams S.E. Beronja S. Pasolli H.A. Fuchs E. Nature. 2011; 470: 353-358Crossref PubMed Scopus (298) Google Scholar). All adult stem cells are not alike, however. This point was hammered home by Hans Clevers (Hubrecht Institute, Netherlands) who described distinct modes of tissue stem cell self-renewal. Clevers and colleagues have previously shown that, unlike some other organ sites, intestinal stem cells undergo symmetric cell divisions followed by stochastic determination of daughter stem cells, ultimately remaining as such or differentiating (Simons and Clevers, 2011Simons B.D. Clevers H. Cell. 2011; 145: 851-862Abstract Full Text Full Text PDF PubMed Scopus (320) Google Scholar). Using multicolor lineage tracing, it was shown that each crypt unit becomes monoclonal on a random basis, consistent with a model for neutral competition between stem cells. Now, Dr. Clevers' group has used compound mutants of LGR4/5 to determine that Wnt signaling, triggered by R-spondin1, is a critical downstream pathway (de Lau et al., 2011de Lau W. Barker N. Low T.Y. Koo B.K. Li V.S. Teunissen H. Kujala P. Haegebarth A. Peters P.J. van de Wetering M. et al.Nature. 2011; 476: 293-297Crossref PubMed Scopus (840) Google Scholar). Swathi Yadlapilli (Yamashita laboratory, University of Michigan, USA) asked the provocative question of whether Drosophila male germline stem cells (GSCs) retain only a subset of chromosomes asymmetrically and used novel techniques to track segregation of individual chromosomes in vivo. While they did not find generalized asymmetric segregation of chromosomes during stem cell division, their novel techniques revealed a preferential segregation of one strand of the Y chromosome in GSCs (Yadlapalli et al., 2011Yadlapalli S. Cheng J. Yamashita Y.M. J. Cell Sci. 2011; 124: 933-939Crossref PubMed Scopus (37) Google Scholar). The functional consequences of stem-cell-like behavior of tumor cells were discussed by Pier Paolo di Fiore (Instituto FIRC di Oncologia, Italy). Specifically, the stem-cell-like fraction of mammary tumors was shown to revert to a pattern of predominantly symmetric cell divisions due to loss of p53, as shown by partitioning of NUMB to both daughter cells and using a live cell stain (Pece et al., 2011Pece S. Confalonieri S. Romano R.R. Di Fiore P.P. Biochim. Biophys. Acta. 2011; 1815: 26-43PubMed Google Scholar). By skipping asymmetric cell division, the tumor is able to acquire bulk and becomes resistant to therapy. In the same vein, Juergen Knoblich reviewed the pivotal role of spindle polarity in Drosophila neuroblasts. His laboratory has shown that disruption of the machinery that maintains polarity leads to tumor formation (Neumüller et al., 2011Neumüller R.A. Richter C. Fischer A. Novatchkova M. Neumüller K.G. Knoblich J.A. Cell Stem Cell. 2011; 8: 580-593Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar). In his lecture, John Dick (University Health Network, Canada) touched on two major themes: that of identifying and profiling single-cell clones of functionally pure human HSCs and how to model the clonal diversity of cancer stem cells in leukemia. A major milestone was recently achieved when Dick's group linked CD49f expression with human HSCs and achieved long-term mulitilineage engraftment of single human cells in immune-compromised mice, using a sorting strategy based on Thy1+Rhodamine123loCD49f+ (Notta et al., 2011aNotta F. Doulatov S. Laurenti E. Poeppl A. Jurisica I. Dick J.E. Science. 2011; 333: 218-221Crossref PubMed Scopus (514) Google Scholar). In an illuminating study of the clonality of leukemia, Dr. Dick's group recently found, by tracking DNA copy number alterations, that acute lymphocytic leukemias follow a nonlinear, branching pattern of evolution. Loss of CDKN2A/B was associated with increased aggressiveness and competitiveness of leukemia-initiating cells (Notta et al., 2011bNotta F. Mullighan C.G. Wang J.C. Poeppl A. Doulatov S. Phillips L.A. Ma J. Minden M.D. Downing J.R. Dick J.E. Nature. 2011; 469: 362-367Crossref PubMed Scopus (371) Google Scholar). Alysson Muotri (University of California, San Diego, USA) had previously showed increased de novo L1 retrotransposition insertions in iPSC-derived neurons from Rett Syndrome patients. His laboratory recently found that common defects in neuronal function were observed in iPSC-derived neurons from Rett Syndrome patients and other autism spectrum disorder patients (Marchetto et al., 2010Marchetto M.C. Carromeu C. Acab A. Yu D. Yeo G.W. Mu Y. Chen G. Gage F.H. Muotri A.R. Cell. 2010; 143: 527-539Abstract Full Text Full Text PDF PubMed Scopus (944) Google Scholar). Michael McConnell (Salk Institute, USA) provided a succinct review of both known and unconventional sources of interindividual genetic variation. He is employing novel, single-cell-based approaches to quantify mosaicism in the brain. An understanding of somatic mosaicism is highly relevant to the future prospects of iPSC-based therapy, because a similar and perhaps more robust phenomenon occurs in cultured cells. Athurva Gore (University of California, San Diego, USA) described a study revealing substantial genetic variation that arises as a consequence of selection and cloning of primary cells in culture and also generation of iPSCs. Similarly, Uri Ben-David (The Hebrew University, Israel) discussed the incidence of karyotypic abnormalities in human iPSCs and derivative cells lines. Such aneuploidy apparently can arise either from preexisting defects in the parental cells or from de novo events during subsequent culture (Mayshar et al., 2010Mayshar Y. Ben-David U. Lavon N. Biancotti J.C. Yakir B. Clark A.T. Plath K. Lowry W.E. Benvenisty N. Cell Stem Cell. 2010; 7: 521-531Abstract Full Text Full Text PDF PubMed Scopus (553) Google Scholar). With the goal of rejuvenating aging muscle, Irina Conboy (University of California, Berkeley) related how stem-cell-driven regenerative capacity is highly dependent on environmental or niche-derived factors (Conboy et al., 2011Conboy I.M. Yousef H. Conboy M.J. Aging. 2011; 3: 555-563PubMed Google Scholar). She hypothesized that muscle stem cells remain young while the surrounding niche ages. This theme was also raised by Amy Wagers (Harvard University, USA), who described the potential for cultured muscle satellite cells as a tool in the discovery of new bioactive molecules for muscle diseases (Shadrach and Wagers, 2011Shadrach J.L. Wagers A.J. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2011; 366: 2297-2306Crossref PubMed Scopus (69) Google Scholar). The biochemical modulation of transcription factor activity in muscle satellite cell differentiation was discussed by Michael Rudnicki (Ottawa Hospital Research Institute, Canada). A novel application for iPSCs described at the meeting is the modeling of autoinflammatory disorders. This strategy was taken by Takayuki Tanaka and colleagues (Kyoto University, Japan) who found that a substantial fraction of chronic infantile neurological cutaneous and articular syndrome (CINCA) cases are due to somatic mosaic NLRP3 mutations, leading to both cell-autonomous and non-cell-autonomous macrophage-dependent effects in a dominant manner (Tanaka et al., 2011Tanaka N. Izawa K. Saito M.K. Sakuma M. Oshima K. Ohara O. Nishikomori R. Morimoto T. Kambe N. Goldbach-Mansky R. et al.Arthritis Rheum. 2011; Google Scholar). Shinya Yamanaka (Kyoto University, Japan) presented work from his laboratory, which continues to refine the reprogramming technology he developed. Although induction of pluripotency is most efficient when cMyc is used, the resulting cells have substantial, persistent oncogenic potential, even after their differentiation. To overcome this problem, his laboratory considered factors that were involved in early reprogramming events in the embryo. In the course of those studies, they discovered that the factor Glis1 compensates very effectively for cMyc, and without the oncogenic side-effects (Maekawa et al., 2011Maekawa M. Yamaguchi K. Nakamura T. Shibukawa R. Kodanaka I. Ichisaka T. Kawamura Y. Mochizuki H. Goshima N. Yamanaka S. Nature. 2011; 474: 225-229Crossref PubMed Scopus (272) Google Scholar). In this way, his studies argue that continued study of the early embryo will help improve the safety and efficiency of reprogramming technologies. Although all present were galvanized by the rapid progress in stem cell science that was reported at this year's meeting, the important and weighty task of beginning to move these findings in a more translational direction was on the minds of many participants. The importance of continuing to focus on the fulfillment of the clinical promise of stem cell research was reinforced by a deeply moving presentation from eloquent patient advocate and journalist Charles Sabine. In an instant, the audience was transported from the shoes of the bench researcher to those of the patient or the family member who is attempting to grapple with the unthinkable reality of a terminal illness, such as Huntington's disease. At a meeting brimming with exceptional science and the promise of new clinical strategies, it was not only humbling and sobering but also inspiring to hear the grace and resolve he has marshaled against difficult if not impossible circumstances. In particular, he spoke of the importance of hope in the lives of those struggling with disease. Inspiringly, he charged the stem cell community with doing all that it could to help maintain the hope of people like himself. Hopefully, Sabine and patient advocates like him will be encouraged by the metered but consistent advance of stem cell technologies toward the clinic that were reported at this year's meeting. This year, some of the most exciting progress continued to be in the development of new therapies for those suffering from disease- or injury-related blindness. Notably, Michele De Luca (University of Milan, Italy) described progress that he and collaborator Graziella Pellegrini have made in the area of delivering autologous limbal stem cells to treat corneal degeneration following ocular burns. Cultured, autologous limbal cells are surgically implanted back into the limbus of the patient's damaged eye. This year, he reported the results from clinical studies of 112 such transplants. Remarkably, in more than 75% of cases, corneal regeneration was restored and stable for as much as 10 years, attributed to p63+ holoclones observed in the limbal outgrowths (Rama et al., 2010Rama P. Matuska S. Paganoni G. Spinelli A. De Luca M. Pellegrini G. N. Engl. J. Med. 2010; 363: 147-155Crossref PubMed Scopus (725) Google Scholar). A promising and proximal application of human ESCs is in the treatment of macular degeneration. Peter Coffey (University College London, UK) described his progress toward delivering a therapy for macular degeneration based on transplantation of human ESC-derived pigmented retinal epithelial cells. His team has been carrying out promising preclinical trials in rat models. In addition, he unveiled an exciting new surgical procedure that might be used to deliver the cells in a noninvasive manner that should result in an outpatient treatment. If pluripotent stem cells, either iPSCs or ESCs, are ever going to become viable therapies on a large scale, then it will be critical to be able to grow and differentiate them on a massive scale. Peter Zandstra (University of Toronto, Canada) described his lab's efforts to overcome this roadblock between basic science and the clinic. Remarkably, he showed that it might be possible to grow large volumes of pluripotent stem cell lines in suspension and even differentiate them “in line” without taking them out of suspension. Christopher Breuer (Yale University School of Medicine, USA) described early clinical trials of a tissue-engineered vascular graft for the treatment of congenital heart defects, reiterating the need to transfer knowledge back to the laboratory to enhance the clinical strategy. He described the identification of macrophages as both the culprit in stenosis, a complication seen in a number of patients, and the driver of neovessel formation, a result that raises an approach using a cell-free biomimetic scaffold to enhance the innate regenerative mechanisms while minimizing the risk of occlusion (Hibino et al., 2011Hibino N. Yi T. Duncan D.R. Rathore A. Dean E. Naito Y. Dardik A. Kyriakides T. Madri J. Pober J.S. et al.FASEB J. 2011; Google Scholar). The final afternoon plenary session was punctuated by the presentation of a new award, the McEwen Centre Award for Innovation. No one could possibly debate the worthiness of this year's winners: Kazutoshi Takahashi and Shinya Yamanaka of Kyoto University, Japan for their development of methods for inducing pluripotency and the resulting effect that their method is beginning to have on the development of new cellular models of disease. Particularly moving were the words of Takahashi during his acknowledgment. He began in a characteristically understated way by saying, “I don't see what the big deal is. I just did a transduction,” before, more emotionally, confessing, “But seriously, these factors, they reprogrammed my life.” It was a moving moment and a sentiment that was likely shared by many in the audience. There can be no doubt that their experiment fundamentally changed the course of stem cell research and developmental biology, with far-reaching consequences for medicine, perhaps in ways we do not yet even imagine. The heartfelt remarks of Takahashi were then followed by a rousing session that focused on the regulator networks that govern stem cell behavior. In this session Rick Young (Massachusetts Institute of Technology, USA) and Stuart Orkin (Children's Hospital Boston, USA) described the identification of mechanisms that regulate the switch between self-renewal and differentiation in pluripotent stem cells, while Judy Lieberman (Harvard Medical School, USA) conveyed the results of a recent genome-wide siRNA screen she had performed to identify inhibitors of breast-cancer-tumor-initiating cells. This session was capped by the Anne McLaren Memorial Lecture, delivered by Nicole Le Douarin (Acadamie Des Sciences, France). In her talk, she outlined experiments carried out by her lab aimed at studying the properties of the neural crest. In these elegant studies, which relied heavily on approaches such as the generation of quail-chick chimeras, she showed that a large proportion of neural crest progenitors are multipotent stem cells with the capacity to differentiate down neural, melanocytic, and osteocytic lineages. The recognition of Takahashi and Yamanaka from Kyoto, Japan in the final session was also a fitting close for the gathering, dovetailing nicely into the 2012 Annual Meeting, when the society will once again convene on the eastern edge of the pacific rim: the Pacifico Yokohama Convention Center in Yokohama, Japan. When the society gathers again, we are sure to hear more about how stem cells are changing the face of science, our understanding of disease, and the development of new therapeutics.
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