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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2513-2521. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-08-2955. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2955v1 103/7/2513    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, C. C. Articles by Lodish, H. F. Search for Related Content PubMed PubMed Citation Articles by Zhang, C. C. Articles by Lodish, H. F. Related Collections Hematopoiesis and Stem Cells Signal Transduction Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells Cheng Cheng Zhang, and Harvey F. Lodish From the Whitehead Institute for Biomedical Research, Cambridge, MA; and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA. Hematopoietic stem cells (HSCs) undergo dramatic expansion during fetal liver development, but attempts to expand their numbers ex vivo have failed. We hypothesized that unidentified fetal liver cells produce growth factors that support HSC proliferation. Here we describe a novel population of CD3+ and Ter119- day-15 fetal liver cells that support HSC expansion in culture, as determined by limiting dilution mouse reconstitution analyses. DNA array experiments showed that, among other proteins, insulin-like growth factor 2 (IGF-2) is specifically expressed in fetal liver CD3+ cells but not in several cells that do not support HSCs. Treatment of fetal liver CD3+Ter119- cells with anti–IGF-2 abrogated their HSC supportive activity, suggesting that IGF-2 is the key molecule produced by these cells that stimulates HSC expansion. All mouse fetal liver and adult bone marrow HSCs express receptors for IGF-2. Indeed, when combined with other growth factors, IGF-2 supports a 2-fold expansion of day-15 fetal liver Lin-Sca-1+c-Kit+ long-term (LT)–HSC numbers. Thus, fetal liver CD3+Ter119- cells are a novel stromal population that is capable of supporting HSC expansion, and IGF-2, produced by these cells, is an important growth factor for fetal liver and, as we show, adult bone marrow HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Huynh, S. Iizuka, M. Kaba, O. Kirak, J. Zheng, H. F. Lodish, and C. C. Zhang Insulin-Like Growth Factor-Binding Protein 2 Secreted by a Tumorigenic Cell Line Supports Ex Vivo Expansion of Mouse Hematopoietic Stem Cells Stem Cells, June 1, 2008; 26(6): 1628 - 1635. [Abstract] [Full Text] [PDF] C. C. Zhang, M. Kaba, S. Iizuka, H. Huynh, and H. F. Lodish Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation Blood, April 1, 2008; 111(7): 3415 - 3423. [Abstract] [Full Text] [PDF] S. Noda, K. Horiguchi, H. Ichikawa, and H. Miyoshi Repopulating Activity of Ex Vivo-Expanded Murine Hematopoietic Stem Cells Resides in the CD48-c-Kit+Sca-1+Lineage Marker- Cell Population Stem Cells, March 1, 2008; 26(3): 646 - 655. [Abstract] [Full Text] [PDF] A. Kaneda, C. J. Wang, R. Cheong, W. Timp, P. Onyango, B. Wen, C. A. Iacobuzio-Donahue, R. Ohlsson, R. Andraos, M. A. Pearson, et al. Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk PNAS, December 26, 2007; 104(52): 20926 - 20931. [Abstract] [Full Text] [PDF] J. A. Martinez-Agosto, H. K.A. Mikkola, V. Hartenstein, and U. Banerjee The hematopoietic stem cell and its niche: a comparative view Genes & Dev., December 1, 2007; 21(23): 3044 - 3060. [Abstract] [Full Text] [PDF] C. Wang, P. W. Faloon, Z. Tan, Y. Lv, P. Zhang, Y. Ge, H. Deng, and J.-W. Xiong Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation Blood, November 15, 2007; 110(10): 3601 - 3609. [Abstract] [Full Text] [PDF] M. B. Bowie, D. G. Kent, M. R. Copley, and C. J. Eaves Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells Blood, June 1, 2007; 109(11): 5043 - 5048. [Abstract] [Full Text] [PDF] L. Soroceanu, S. Kharbanda, R. Chen, R. 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