Stem Cells in the Spotlight Again

Once again, hematopoietic stem cells (HSC) were discussed extensively in five simultaneous oral sessions yesterday that offered a smorgasboard of topics including animal models and developmental biology, experimental transplantation, modulators of stem cell self renewal, gene therapy and stem cell engineering, and stem cell plasticity. Fortunately for stem cell biologists, these sessions were dispersed throughout the day, making it possible to attend many of the sessions without painful conflicts. So, what was covered in these 30 exciting presentations? Given our space limitations in this publication, we will cover as many topics as possible, and apologize for those we will miss.

Zebrafish models dominated the Animal Models session. A new zebrafish model was used to demonstrate that BMP signaling is required for LMO2+ cells for normal development but is not required in primitive erythroid cells once expression of GATA-1 is activated. A new model for yolk sac hematopoiesis dependent on suppression of Retinoic acid signaling by the cdx-hox pathway was revealed that may explain how hox genes control the spatiotemporal formation of hematopoiesis tissues and affect pathogenesis of leukemias. Dr. Verfaillie’s group from the University of Minnesota also used zebrafish to describe a high-throughput functional genomics screen to functionally validate differentially expressed genes in highly purified populations of primitive human HSC and to determine how SPRY4, a member of the SPRY proteins which are antagonists of the FGF, EGF, and VEGF pathways, participated in hematopoiesis and the specification of the hemangioblast.

The Experimental Transplantation session dealt with a broad repertoire of very interesting topics. Non-hematopoietic stem cells, as in neuronal stem cells, were discussed in the context of their in utero transplantation in mice with lysosomal storage disease. A new strain of NOD/SCID mice, the NOD-scid IL2rnull mouse, which is “non-leaky,” lives up to 16 months, and is resistant to the development of lymphomas, made its debut. Continuing with the theme of NOD/SCID mice, the effect of the use of anti-CD122 antibodies prior to transplantation in conjunction with intrafemoral introduction of graft cells was shown to promote the engraftment of the rapid- SRC (R-SRC). The recently described aldehyde dehydrogenase-based fractionation procedure in association with CD133 was used to define a highly enriched group of cells with multilineage in vivo differentiation capacity. There was even room in this session for summarizing the NHLBI experience with Fludara-bine-based nonmyeloablative allo-transplantation and the demonstration that this clinical approach can achieve excellent donor engraftment and long-term disease-free survival.

HoxB4 received a good share of the discussions in these sessions, including a presentation describing the interplay between the regulatory elements of hematopoiesis HoxB4 and Pbx-1, self-renewal, and the microenvironment. Other presentations reflecting on self-renewal and specification of lineage commitment included an interesting series of single cell studies that challenge the concepts of the already described common lymphoid or myeloid precursors. These studies support the instructive role of cytokines in the restriction of the lymphoid potential of stem cells that was drawn from observing different profiles of lymphoid and myeloid reconstitution patterns in mice transplanted with single daughter cells produced from one stem cell in two different cytokine cocktails.

Finally, the field of stem cell plasticity continues to describe new and stirring findings. In two studies in the stem cell plasticity session, scientists from two groups provided evidence that normal and tumor fibroblasts are hematopoietic in origin, warranting a re-examination of the relationship between hematopoietic stem cells and mesenchymal stem cells.