Submitted to: Blood
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2003
Publication Date: 6/12/2003
Citation: Nadin, B.M., Goodell, M.A., Hirschi, K.K. 2003. Phenotype and hematopoietic potential of side population cells throughout embryonic development. Blood. 102(7):2436-2443. Interpretive Summary: The mechanisms by which stem cells give rise to differentiated body cells are not well known, and are important to the development of the therapeutic potential of stem cells. It is well known that bone marrow stem cells can give rise to blood cells in mice, but the potential of yolk sac stem cells is relatively unknown. Our study examined distinct genetic populations of mice in various stages of fetal development. Results of this research suggest that yolk sac stem cells have the capacity to make blood cells, as do bone marrow stem cells. Our findings suggest the possibility of yolk sac stem cell transplantation to produce clinical therapies for human blood disease.
Technical Abstract: Adult murine bone marrow hematopoietic stem cells (HSCs) can be purified by sorting Hoechst 33342-extruding side population (SP) cells. Herein we investigated whether SP cells reside within embryonic tissues and exhibit hematopoietic progenitor activity. We isolated yolk sac (YS) and embryonic tissues 7.5 to 11.5 days after coitus (dpc), resolved an SP in each, and demonstrated that these SP cells exhibit distinct phenotypic and functional characteristics throughout development. YS and embryonic SP isolated 8.0 dpc expressed vascular endothelial-cadherin (VE-cadherin) and vascular endothelial receptor 2 (Flk-1), markers not expressed by bone marrow SP but expressed by endothelial cells and progenitors. SP at this stage did not express CD45 or produce hematopoietic colonies in vitro. In contrast, SP isolated 9.5 to 11.5 dpc contained a significantly higher proportion of cells expressing cKit and CD45, markers highly expressed by bone marrow SP. Furthermore, YS SP isolated 9.5 to 11.5 dpc demonstrated 40- to 90-fold enrichment for hematopoietic progenitor activity over unfractionated tissue. Our data indicate that YS and embryonic SP cells detected prior to the onset of circulation express the highest levels of endothelial markers and do not generate blood cells in vitro; however, as development progresses, they acquire hematopoietic potential and phenotypic characteristics similar to those of bone marrow SP.