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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4111-4118. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2003-10-3448. This Article Full Text (PDF) All Versions of this Article: 2003-10-3448v1 103/11/4111    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 Muller-Sieburg, C E Articles by Sieburg, H B Search for Related Content PubMed PubMed Citation Articles by Muller-Sieburg, C E Articles by Sieburg, H B Social Bookmarking                   What's this? Submitted October 8, 2003 Accepted February 4, 2004 Myeloid-Biased Hematopoietic Stem Cells have Extensive Self-Renewal Capacity but Generate Diminished Lymphoid Progeny with Impaired IL-7 Responsiveness C E Muller-Sieburg*, R H Cho, L Karlsson, J F Huang, and H B Sieburg Sidney Kimmel Cancer Center, San Diego, CA, USA R.W. Johnson Pharmaceutical, San Diego, CA, USA University of California San Diego, San Diego, CA, USA * Corresponding author; email: cmuller{at}skcc.org. The adult hematopoietic stem cell (HSC) compartment contains a substantial population of linage-biased (Lin-bi) HSCs. Lin-bi HSCs generate cells of all hematopoietic lineages albeit with skewed ratios of lymphoid to myeloid cells. The biased ratios are stable through serial transplantation, demonstrating that Lin-bias is an inherent function of the HSC. To define the mechanisms that cause Lin-bias, the developmental potential of myeloid-biased (My-bi) HSCs was characterized. In serial transplantation experiments, My-bi HSC contributed significantly longer to repopulation than other types of HSCs. The long life span indicates that My-bi HSCs are important for the persistence of HSC function throughout life. My-bi HSCs produce normal levels of myeloid precursors, but reduced levels of precursors for the T and B lymphocyte lineages. Gene array analysis suggested that the lymphoid progeny of My-bi HSCs expresses lowered levels of IL-7 receptor. Indeed, the progeny derived from My-bi HSCs failed to respond to IL-7 in vitro. Thus, My-bi HSCs are programmed for diminished lymphopoiesis via a mechanism that involves a blunted response of its progeny to the central lymphokine IL-7. The data demonstrate that epigenetic regulation on the level of the HSCs can directly affect the number, composition, and function of the mature progeny. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. G. Kent, M. R. Copley, C. Benz, S. Wohrer, B. J. Dykstra, E. Ma, J. Cheyne, Y. Zhao, M. B. Bowie, Y. Zhao, et al. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential Blood, June 18, 2009; 113(25): 6342 - 6350. [Abstract] [Full Text] [PDF] I. Roeder, K. Horn, H.-B. Sieburg, R. Cho, C. Muller-Sieburg, and M. Loeffler Characterization and quantification of clonal heterogeneity among hematopoietic stem cells: a model-based approach Blood, December 15, 2008; 112(13): 4874 - 4883. [Abstract] [Full Text] [PDF] R. H. Cho, H. B. Sieburg, and C. E. Muller-Sieburg A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells Blood, June 15, 2008; 111(12): 5553 - 5561. [Abstract] [Full Text] [PDF] V. P. Zediak, I. Maillard, and A. Bhandoola Multiple prethymic defects underlie age-related loss of T progenitor competence Blood, August 15, 2007; 110(4): 1161 - 1167. [Abstract] [Full Text] [PDF] H. B. Sieburg, R. H. Cho, B. Dykstra, N. Uchida, C. J. Eaves, and C. E. Muller-Sieburg The hematopoietic stem compartment consists of a limited number of discrete stem cell subsets Blood, March 15, 2006; 107(6): 2311 - 2316. [Abstract] [Full Text] [PDF] R. Kumar, J. C. Langer, and H.-W. Snoeck Transforming growth factor-beta2 is involved in quantitative genetic variation in thymic involution Blood, March 1, 2006; 107(5): 1974 - 1979. [Abstract] [Full Text] [PDF] A. Sternberg, S. Killick, T. Littlewood, C. Hatton, A. Peniket, T. Seidl, S. Soneji, J. Leach, D. Bowen, C. Chapman, et al. Evidence for reduced B-cell progenitors in early (low-risk) myelodysplastic syndrome Blood, November 1, 2005; 106(9): 2982 - 2991. [Abstract] [Full Text] [PDF] E. Henckaerts, J. C. Langer, J. Orenstein, and H.-W. Snoeck The Positive Regulatory Effect of TGF-{beta}2 on Primitive Murine Hemopoietic Stem and Progenitor Cells Is Dependent on Age, Genetic Background, and Serum Factors J. Immunol., August 15, 2004; 173(4): 2486 - 2493. [Abstract] [Full Text] [PDF]

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