During embryogenesis, the close relationship between hematopoietic stem cells and the developing vascular system suggests the existence of a common precursor cell during early development. In the adult, the bone marrow is the principal site of steady state hematopoiesis. We now show that hematopoiesis can be induced in normal adult blood vessels. Our data demonstrate that the transplantation of segments of adult vena cava or thoracic aorta protects mice from lethal irradiation. Blood vessel derived progenitor cells migrate to the spleens or recipient animals where they give rise to day 14 CFU-S with the same frequency observed following the transplantation of normal bone marrow. Donor derived cells are readily detected in the peripheral blood and spleen of recipient mice and multilineage progeny of these blood vessel derived cells have been demonstrated. In addition, vascular tissue grafts substantially protect host hematopoiesis from the effects of radiation. These findings indicate the presence of a previously unknown reservoir of cells with hematopoietic potential in the blood vessels of normal adult mice. To further evaluate the biologic activity of this cell population(s) we propose to: 1) Characterize the early activation and migration of blood vessel derived cells with hematopoietic activity; 2) Evaluate the functional activity and transplantation potential of blood vessel derived hematopoietic cells and 3) Isolate and characterize populations of phenotypically and functionally defined blood vessel associated stem cells.
| Yao, Huilan; Goldman, Devorah C; Fan, Guang et al. (2015) The Corepressor Rcor1 Is Essential for Normal Myeloerythroid Lineage Differentiation. Stem Cells 33:3304-14 |
| Yao, Huilan; Goldman, Devorah C; Nechiporuk, Tamilla et al. (2014) Corepressor Rcor1 is essential for murine erythropoiesis. Blood 123:3175-84 |
| Cogle, Christopher R; Goldman, Devorah C; Madlambayan, Gerard J et al. (2014) Functional integration of acute myeloid leukemia into the vascular niche. Leukemia 28:1978-1987 |
| Hakki, Morgan; Goldman, Devorah C; Streblow, Daniel N et al. (2014) HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors. Biol Blood Marrow Transplant 20:132-5 |
| Skinner, Amy M; Grompe, Markus; Kurre, Peter (2012) Intra-hematopoietic cell fusion as a source of somatic variation in the hematopoietic system. J Cell Sci 125:2837-43 |
| Umashankar, Mahadevaiah; Petrucelli, Alex; Cicchini, Louis et al. (2011) A novel human cytomegalovirus locus modulates cell type-specific outcomes of infection. PLoS Pathog 7:e1002444 |
| Smith, M Shane; Goldman, Devorah C; Bailey, Alexis S et al. (2010) Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8:284-91 |
| Zhang, Qing-Shuo; Marquez-Loza, Laura; Eaton, Laura et al. (2010) Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. Blood 116:5140-8 |
| Li, Bei; Bailey, Alexis S; Jiang, Shuguang et al. (2010) Endothelial cells mediate the regeneration of hematopoietic stem cells. Stem Cell Res 4:17-24 |
| Goldman, Devorah C; Bailey, Alexis S; Pfaffle, Dana L et al. (2009) BMP4 regulates the hematopoietic stem cell niche. Blood 114:4393-401 |
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