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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0490. This Article Full Text (PDF) All Versions of this Article: 2002-02-0490v1 100/12/3975    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Slayton, W. B Articles by Spangrude, G. J Search for Related Content PubMed PubMed Citation Articles by Slayton, W. B Articles by Spangrude, G. J Social Bookmarking                   What's this? Submitted February 21, 2002 Accepted May 21, 2002 The spleen is a major site of megakaryopoiesis following transplant of murine hematopoietic stem cells William B Slayton*, Ann Georgelas, L J Pierce, Kojo S Elenitoba-Johnson, S S Perry, Melissa Marx, and Gerald J Spangrude Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah, USA Pathology, University of Utah, Salt Lake City, Utah, USA Oncological Sciences, University of Utah, Salt Lake City, Utah, USA; Pathology, University of Utah, Salt Lake City, Utah, USA * Corresponding author; email: bslayton{at}hci.utah.edu. The stem cell pool can be fractionated using the mitochondrial dye, rhodamine-123, into Rholow hematopoietic stem cells and Rhohigh progenitors. Rholow stem cells permanently engraft all lineages, whereas Rhohigh progenitors transiently produce erythrocytes, without significant platelet or granulocyte production. We hypothesized that the inability of the Rhohigh cells to produce platelets in vivo was due to the fact that these cells preferentially engraft in the spleen, and lack marrow engraftment. Initially, we demonstrated that Rhohigh progenitors produced more megakaryocytes in vitro than Rholow stem cells did. To study the activity of the Rholow and Rhohigh subsets in vivo, we used mice allelic at the hemoglobin and glucose phosphate isomerase loci to track donor-derived erythropoiesis and thrombopoiesis. Rholow stem cells contributed to robust and long-term erythroid and platelet engraftment, whereas Rhohigh progenitors contributed only to transient erythroid engraftment, and produced very low numbers of platelets in vivo. Donor-derived megakaryopoiesis occurred at higher densities in the spleen than in the bone marrow in animals receiving Rholow stem cells, and peaked around day 28. Blockade of splenic engraftment using pertussis toxin did not affect the peak of splenic megakaryopoiesis, supporting the hypothesis that these megakaryocytes were derived from progenitors which originated in the bone marrow. These data emphasize that in vitro behavior of hematopoietic progenitor cell subsets does not always predict their behavior following transplantation. This study supports a major role for the spleen in thrombopoiesis following engraftment of transplanted stem cells in irradiated mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. R. Migliaccio, F. Martelli, M. Verrucci, M. Sanchez, M. Valeri, G. Migliaccio, A. M. Vannucchi, M. Zingariello, A. Di Baldassarre, B. Ghinassi, et al. Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation Blood, September 3, 2009; 114(10): 2107 - 2120. [Abstract] [Full Text] [PDF] H. Wang, S. Cnhen, Y. Chen, H. Wang, H. Wu, H. Tang, W. Xiong, J. Ma, Y. Ge, Q. Lu, et al. The role of Tyro 3 subfamily receptors in the regulation of hemostasis and megakaryocytopoiesis Haematologica, May 1, 2007; 92(5): 643 - 650. [Abstract] [Full Text] [PDF] F. Martelli, B. Ghinassi, B. Panetta, E. Alfani, V. Gatta, A. Pancrazzi, C. Bogani, A. M. Vannucchi, F. Paoletti, G. Migliaccio, et al. Variegation of the phenotype induced by the Gata1low mutation in mice of different genetic backgrounds Blood, December 15, 2005; 106(13): 4102 - 4113. [Abstract] [Full Text] [PDF] C. I. Baumann, A. S. Bailey, W. Li, M. J. Ferkowicz, M. C. Yoder, and W. H. Fleming PECAM-1 is expressed on hematopoietic stem cells throughout ontogeny and identifies a population of erythroid progenitors Blood, August 15, 2004; 104(4): 1010 - 1016. [Abstract] [Full Text] [PDF] S. S. Perry, H. Wang, L. J. Pierce, A. M. Yang, S. Tsai, and G. J. Spangrude L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor Blood, April 15, 2004; 103(8): 2990 - 2996. [Abstract] [Full Text] [PDF]

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