Erythroid Potential Found in Hematopoietic Non Self-Renewing Multipotent Progenitors

Friday, October 28, 2011
Hall 1-2 (San Jose Convention Center)
Ana Ibarra , University of California, Santa Cruz, santa cruz, CA
Anna E Beaudin, PhD , Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA
E Camilla Forsberg, PhD , Department of Biomolecular Engineering, University of California, Santa Cruz, Santa cruz, CA
Self-renewing hematopoietic stem cells (HSCs) give rise to all blood cell types.  Understanding the process of differentiation and proliferation of these cells is important for proper implementation of therapeutics.  The accuracy of the classic hematopoietic lineage tree is in question when describing the role that non self-renewing multipotent progenitors (MPPs) play in the output of mature myeloid cells.   Flk2, a tyrosine kinase receptor is crucial for the development and proliferation of hematopoietic cells.  Through the use of lineage-tracing mouse models, it has been found that Flk2 negative myeloid cells develop through a Flk2-positive non self-renewing multipotent progenitor, as opposed to being derived directly from Flk2-negative self-renewing HSCs.  The contribution of non self-renewing MPPs to all hematopoietic cell types and the role of Flk2 in generating mature lineages can be further elucidated by quantifying erythroid reconstitution and survival following injections of the myelo-suppressive agent 5-fluorouracil into mice lacking expression of Flk-2 and wild-type (WT) controls.  A second approach to this concept can be achieved by performing colony-forming unit of the spleen assays in which erythroid potential is quantified by analyzing the formation of erythroid colonies on the spleen of irradiated mice following the transplantation of MPPs and HSCs isolated from Flk2-deficient and WT mice.  Intravenous versus intrasplenic transplantation of cells will also be compared to test the hypothesis that Flk2 readout in both of these assays will provide a better understanding of the erythroid potential of non self-renewing MPPs and the role of Flk2 in generating erythroid lineages.