Cells, niche, fate: meeting report on the 6th International Meeting of the Stem Cell Network North Rhine Westphalia.

In April 2011, leading stem cell researchers from all over the world came together for the 6th International Meeting of the Stem Cell Network North Rhine Westphalia (www .kongress.stammzellen.nrw.de), organized by Hans Schöler (Münster), Oliver Brüstle (Bonn), and Peter Horn (Essen). Notably, more than 600 participants, presenting 136 posters, joined the congress in Essen attracted by the scientific program focussing on ‘‘Homing and migration,’’ ‘‘Cell Fate Specification,’’ and ‘‘Disease Modeling.’’ In addition to these wellestablished topics new sessions dealing with ‘‘Nonhuman Primate Pluripotent Stem Cells’’ and ‘‘Niche, Hypoxia, and Metabolism’’ were integrated into the congress program. This report highlights a few of the most interesting presentations from the broad spectrum of stem cell research. The hematopoietic component of marrow consists predominantly of developing erythrocytes and neutrophils: two lineages that start off as proliferating blasts with a high nuclear-to-cytoplasmic ratio, but go on to develop widely different metabolic characteristics and requirements. The idea presented by Michael Cross (Department of Hematology/ Oncology IZKF, University of Leipzig, Germany) is that hematopoiesis may be organized into metabolic regions of the bone marrow, influenced on the one hand by the relative proximity to arterial or sinusoidal vessels, and on the other hand by the metabolism of the intervening cells. It is now generally accepted that stem cells are maintained in areas in which oxygen tension (and with it oxidative damage) is low. In more active multipotent progenitors, however, hypoxia activates glycolysis and results in differentiation. In comparison, high osmolarity maintains the undifferentiated state while reducing glycolysis and increasing the use of glutamine, consistent with a metabolism biased toward nucleic acid synthesis. In this way, the spatial separation of metabolic pathways in distinct compartments may tailor metabolism to function and avoid the accumulation of potentially toxic products (Cross et al., 2008). Working with hematopoietic stem cells (HSC), Norman Iscove (The Ontario Cancer Institute, University Health Network, Toronto, Canada) presented his data on Gata3, a transcription factor and significant regulator of HSC fate. He could identify strong overexpression of Gata3 transcripts and protein in murine marrow cell fractions comprising 30–85% long-term hematopoietic stem cells (LT-HSC) relative to purified intermediate-term (IT-) HSC (Benveniste et al., 2010). Gata3 transcripts were also most highly expressed in fractions of human cord blood cells comprising 5–10% of cells able to stably reconstitute immunodeficient mice. In Gata3-knockin mice expressing eGFP from the endogenous Gata3 promoter, all LT-HSC were located in eGFP+ cells, whereas all IT-HSC were isolated in nonfluorescent fractions, confirming directly the transcriptional activity of the Gata3 locus in LTbut not in IT-HSC. Gata3 protein was cytoplasmic in freshly isolated LT-HSC in the quiescent state, but translocated to the nucleus when he induced the cells to cycle actively in culture. In mice engineered to delete Gata3 conditionally after induction of Cre recombinase, deletion in the steady state had no significant early or late effects on hematopoiesis, as expected, because Gata3 should remain cytoplasmic in quiescent HSC. In marked contrast he could show, when deleted cells from such mice were injected into irradiated recipients they strongly outcompeted control cells expressing Gata3, and this advantage expanded when marrow cells from these primary recipients were used to reconstitute secondary recipients. The HSC autonomy of the regenerative advantage was confirmed in experiments in which Gata3 deletion was induced after injection of conditionally deletable cells together with wild-type cells into wild-type hosts prior to induction of Cre recombinase followed by a test for competitive advantage in secondary hosts. These experiments establish Gata3 acting to constrain the extent of self-renewal/expansion in dividing LT-HSC. The presentation from Denis Corbeil (Biotec, Technische Universität Dresden, Germany) was focused on the role of prominin-1, a cholesterol-binding protein (alias CD133), that is widely used as a stem and cancer stem cell marker. He and others previously showed that in both stem cell types, prominin-1 is either symmetrically/asymmetrically distributed during cell division (Fonseca et al., 2008; Giebel et al., 2004) or released into the extracellular milieu in association with small membrane vesicles during the process of cellular differentiation. However, molecular mechanisms underlying these phenomena seem to differ according to the origin of the stem/progenitor cells. In neuroepithelial cells, the segregation of the prominin-1-containing apical plasma membrane that is determined by the orientation of the cleavage plane appears to be the essential cause of its symmetrically/