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Blood, 1 December 2003, Vol. 102, No. 12, pp. 3938-3946. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-05-1479. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1479v1 102/12/3938    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Zhang, J. Articles by Lodish, H. F. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Lodish, H. F. Related Collections Hematopoiesis and Stem Cells Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry–based novel culture system Jing Zhang, Merav Socolovsky, Alec W. Gross, and Harvey F. Lodish From the Whitehead Institute for Biomedical Research, Cambridge, MA; and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. Ras signaling plays an important role in erythropoiesis. Its function has been extensively studied in erythroid and nonerythroid cell lines as well as in primary erythroblasts, but inconclusive results using conventional erythroid colony-forming unit (CFU-E) assays have been obtained concerning the role of Ras signaling in erythroid differentiation. Here we describe a novel culture system that supports terminal fetal liver erythroblast proliferation and differentiation and that closely recapitulates erythroid development in vivo. Erythroid differentiation is monitored step by step and quantitatively by a flow cytometry analysis; this analysis distinguishes CD71 and TER119 double-stained erythroblasts into different stages of differentiation. To study the role of Ras signaling in erythroid differentiation, different H-ras proteins were expressed in CFU-E progenitors and early erythroblasts with the use of a bicistronic retroviral system, and their effects on CFU-E colony formation and erythroid differentiation were analyzed. Only oncogenic H-ras, not dominant-negative H-ras, reduced CFU-E colony formation. Analysis of infected erythroblasts in our newly developed system showed that oncogenic H-ras blocks terminal erythroid differentiation, but not through promoting apoptosis of terminally differentiated erythroid cells. Rather, oncogenic H-ras promotes abnormal proliferation of CFU-E progenitors and early erythroblasts and supports their erythropoietin (Epo)–independent growth. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. A. Steiner, Y. Maksimova, V. Schulz, C. Wong, D. Raha, M. C. Mahajan, S. M. Weissman, and P. G. Gallagher Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes Mol. Cell. Biol., October 15, 2009; 29(20): 5399 - 5412. [Abstract] [Full Text] [PDF] A. D. Wood, E. Chen, I. J. Donaldson, S. Hattangadi, K. A. Burke, M. A. Dawson, D. Miranda-Saavedra, H. F. Lodish, A. R. Green, and B. Gottgens ID1 promotes expansion and survival of primary erythroid cells and is a target of JAK2V617F-STAT5 signaling Blood, August 27, 2009; 114(9): 1820 - 1830. [Abstract] [Full Text] [PDF] F. Marques-Garcia, N. Ferrandiz, R. Fernandez-Alonso, L. 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Lefebvre Sox6 cell-autonomously stimulates erythroid cell survival, proliferation, and terminal maturation and is thereby an important enhancer of definitive erythropoiesis during mouse development Blood, August 15, 2006; 108(4): 1198 - 1207. [Abstract] [Full Text] [PDF] E. Ferretti, J. C. Villaescusa, P. Di Rosa, L. C. Fernandez-Diaz, E. Longobardi, R. Mazzieri, A. Miccio, N. Micali, L. Selleri, G. Ferrari, et al. Hypomorphic Mutation of the TALE Gene Prep1 (pKnox1) Causes a Major Reduction of Pbx and Meis Proteins and a Pleiotropic Embryonic Phenotype Mol. Cell. Biol., August 1, 2006; 26(15): 5650 - 5662. [Abstract] [Full Text] [PDF] Y. Liu, R. Pop, C. Sadegh, C. Brugnara, V. H. Haase, and M. Socolovsky Suppression of Fas-FasL coexpression by erythropoietin mediates erythroblast expansion during the erythropoietic stress response in vivo Blood, July 1, 2006; 108(1): 123 - 133. [Abstract] [Full Text] [PDF] T. Ito, N. Arimitsu, M. Takeuchi, N. Kawamura, M. Nagata, K. Saso, N. Akimitsu, H. Hamamoto, S. Natori, A. Miyajima, et al. Transcription Elongation Factor S-II Is Required for Definitive Hematopoiesis Mol. Cell. Biol., April 15, 2006; 26(8): 3194 - 3203. [Abstract] [Full Text] [PDF] P. G. Gallagher, M. O. Arcasoy, S. E. Vayda, H. K. Dressman, J. J. Bieker, and D. M. Bodine A Differentiation Block in Erythroid Cells Lacking Erythroid Krupple-Like Factor (EKLF). Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 526 - 526. [Abstract] B. Bonnesen, C. Orskov, S. Rasmussen, P. J. Holst, J. P. Christensen, K. W. Eriksen, K. Qvortrup, N. Odum, and T. Labuda MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver Blood, November 15, 2005; 106(10): 3396 - 3404. [Abstract] [Full Text] [PDF] J. Zhang and H. F. Lodish Identification of K-ras as the major regulator for cytokine-dependent Akt activation in erythroid progenitors in vivo PNAS, October 11, 2005; 102(41): 14605 - 14610. [Abstract] [Full Text] [PDF] S. 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