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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3615-3623. Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-11-4089. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2003-11-4089v1 103/10/3615    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 Back, J. Articles by Chan, S. Search for Related Content PubMed PubMed Citation Articles by Back, J. Articles by Chan, S. Related Collections Perspectives Hematopoiesis and Stem Cells Immunobiology Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS PU.1 determines the self-renewal capacity of erythroid progenitor cells Jonathan Back, Andrée Dierich, Corinne Bronn, Philippe Kastner, and Susan Chan From the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS-INSERM-ULP, ILLKIRCH CEDEX, France. PU.1 is a hematopoietic-specific transcriptional activator that is absolutely required for the differentiation of B lymphocytes and myeloid-lineage cells. Although PU.1 is also expressed by early erythroid progenitor cells, its role in erythropoiesis, if any, is unknown. To investigate the relevance of PU.1 in erythropoiesis, we produced a line of PU.1-deficient mice carrying a green fluorescent protein reporter at this locus. We report here that PU.1 is tightly regulated during differentiation—it is expressed at low levels in erythroid progenitor cells and down-regulated upon terminal differentiation. Strikingly, PU.1-deficient fetal erythroid progenitors lose their self-renewal capacity and undergo proliferation arrest, premature differentiation, and apoptosis. In adult mice lacking one PU.1 allele, similar defects are detected following stress-induced erythropoiesis. These studies identify PU.1 as a novel and critical regulator of erythropoiesis and highlight the versatility of this transcription factor in promoting or preventing differentiation depending on the hematopoietic lineage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Olive, N. Wagner, S. Chan, P. Kastner, C. Vannetti, F. Cuzin, and M. Rassoulzadegan PU.1 (Sfpi1), a pleiotropic regulator expressed from the first embryonic stages with a crucial function in germinal progenitors Development, November 1, 2007; 134(21): 3815 - 3825. [Abstract] [Full Text] [PDF] P. Rimmele, O. Kosmider, P. Mayeux, F. Moreau-Gachelin, and C. Guillouf Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation Blood, April 1, 2007; 109(7): 3007 - 3014. [Abstract] [Full Text] [PDF] A. Vegiopoulos, P. Garcia, N. Emambokus, and J. Frampton Coordination of erythropoiesis by the transcription factor c-Myb Blood, June 15, 2006; 107(12): 4703 - 4710. [Abstract] [Full Text] [PDF] D. Metcalf, A. Dakic, S. Mifsud, L. Di Rago, L. Wu, and S. Nutt Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia PNAS, January 31, 2006; 103(5): 1486 - 1491. [Abstract] [Full Text] [PDF] A. Dumortier, R. Jeannet, P. Kirstetter, E. Kleinmann, M. Sellars, N. R. dos Santos, C. Thibault, J. Barths, J. Ghysdael, J. A. Punt, et al. Notch Activation Is an Early and Critical Event during T-Cell Leukemogenesis in Ikaros-Deficient Mice Mol. Cell. Biol., January 1, 2006; 26(1): 209 - 220. [Abstract] [Full Text] [PDF] M. A. Juarez, F. Su, S. Chun, M. J. Kiel, and S. E. Lyons Distinct Roles for SCL in Erythroid Specification and Maturation in Zebrafish J. Biol. Chem., December 16, 2005; 280(50): 41636 - 41644. [Abstract] [Full Text] [PDF] H. Iwasaki, C. Somoza, H. Shigematsu, E. A. Duprez, J. Iwasaki-Arai, S.-i. Mizuno, Y. Arinobu, K. Geary, P. Zhang, T. Dayaram, et al. Distinctive and indispensable roles of PU.1 in maintenance of hematopoietic stem cells and their differentiation Blood, September 1, 2005; 106(5): 1590 - 1600. [Abstract] [Full Text] [PDF] A. Dakic, D. Metcalf, L. Di Rago, S. Mifsud, L. Wu, and S. L. Nutt PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis J. Exp. Med., May 2, 2005; 201(9): 1487 - 1502. [Abstract] [Full Text] [PDF] S. L. Nutt, D. Metcalf, A. D'Amico, M. Polli, and L. Wu Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors J. Exp. Med., January 18, 2005; 201(2): 221 - 231. [Abstract] [Full Text] [PDF]

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