SEARCH:   Advanced

Blood, 15 May 2007, Vol. 109, No. 10, pp. 4191-4199. Prepublished online as a Blood First Edition Paper on January 23, 2007; DOI 10.1182/blood-2006-10-054213. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-054213v1 109/10/4191    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 Sanyal, M. Articles by Cleary, M. L. Search for Related Content PubMed PubMed Citation Articles by Sanyal, M. Articles by Cleary, M. L. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS B-cell development fails in the absence of the Pbx1 proto-oncogene Mrinmoy Sanyal1, James W. Tung2, Holger Karsunky1, Hong Zeng1, Licia Selleri3, Irving L. Weissman1, Leonore A. Herzenberg2, and Michael L. Cleary1 1 Department of Pathology and 2 Department of Genetics, Stanford University School of Medicine, Stanford, CA; 3 Department of Cell and Developmental Biology, Cornell University Medical School, New York, NY Pbx1, a homeodomain transcription factor that was originally identified as the product of a proto-oncogene in acute pre-B–cell leukemia, is a global regulator of embryonic development. However, embryonic lethality in its absence has prevented an assessment of its role in B-cell development. Here, using Rag1-deficient blastocyst complementation assays, we demonstrate that Pbx1 null embryonic stem (ES) cells fail to generate common lymphoid progenitors (CLPs) resulting in a complete lack of B and NK cells, and a partial impairment of T-cell development in chimeric mice. A critical role for Pbx1 was confirmed by rescue of B-cell development from CLPs following restoration of its expression in Pbx1-deficient ES cells. In adoptive transfer experiments, B-cell development from Pbx1-deficient fetal liver cells was also severely compromised, but not erased, since transient B lymphopoiesis was detected in Rag-deficient recipients. Conditional inactivation of Pbx1 in pro-B (CD19+) cells and thereafter revealed that Pbx1 is not necessary for B-cell development to proceed from the pro-B–cell stage. Thus, Pbx1 critically functions at a stage between hematopoietic stem cell development and B-cell commitment and, therefore, is one of the earliest-acting transcription factors that regulate de novo B-lineage lymphopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Dudakov, G. L. Goldberg, J. J. Reiseger, A. P. Chidgey, and R. L. Boyd Withdrawal of Sex Steroids Reverses Age- and Chemotherapy-Related Defects in Bone Marrow Lymphopoiesis J. Immunol., May 15, 2009; 182(10): 6247 - 6260. [Abstract] [Full Text] [PDF] T.-S. Huang, J.-Y. Hsieh, Y.-H. Wu, C.-H. Jen, Y.-H. Tsuang, S.-H. Chiou, J. Partanen, H. Anderson, T. Jaatinen, Y.-H. Yu, et al. Functional Network Reconstruction Reveals Somatic Stemness Genetic Maps and Dedifferentiation-Like Transcriptome Reprogramming Induced by GATA2 Stem Cells, May 1, 2008; 26(5): 1186 - 1201. [Abstract] [Full Text] [PDF] X. Chen, B. L. Esplin, K. P. Garrett, R. S. Welner, C. F. Webb, and P. W. Kincade Retinoids Accelerate B Lineage Lymphoid Differentiation J. Immunol., January 1, 2008; 180(1): 138 - 145. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020