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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2968-2975. Prepublished online as a Blood First Edition Paper on December 6, 2005; DOI 10.1182/blood-2005-05-2138. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-2138v1 107/7/2968    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 Takizawa, H. Articles by Takaki, S. Search for Related Content PubMed PubMed Citation Articles by Takizawa, H. Articles by Takaki, S. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Stem Cells in Hematology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  STEM CELLS IN HEMATOLOGY Enhanced engraftment of hematopoietic stem/progenitor cells by the transient inhibition of an adaptor protein, Lnk Hitoshi Takizawa, Chiyomi Kubo-Akashi, Ikuo Nobuhisa, Sang-Mo Kwon, Masanori Iseki, Tetsuya Taga, Kiyoshi Takatsu, and Satoshi Takaki From the Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo; and Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan. Hematopoietic stem cells (HSCs) are the key elements responsible for maintaining blood-cell production throughout life and for lymphohematopoietic reconstitution following bone marrow (BM) transplantation. Enhancement of the engrafting potential and expansion capabilities of HSCs as well as hematopoietic progenitor cells (HPCs) has been a long-time desire as a means of reducing the risks and difficulties that accompany BM transplantation. The ability of HSCs/HPCs to reconstitute the hematopoietic system of irradiated hosts is negatively regulated by an intracellular adaptor protein, Lnk. Here we have identified the functional domains of Lnk and developed a dominant-negative (DN) Lnk mutant that inhibits the functions of Lnk endogenously expressed in the HSCs/HPCs and thereby potentiates the HSCs/HPCs for engraftment. Importantly, even transient expression of DN-Lnk in HSCs/HPCs facilitated their engraftment under nonmyeloablative conditions and fully reconstituted the lymphoid compartments of immunodeficient host animals. HPCs expressing DN-Lnk were efficiently trapped by immobilized vascular cell adhesion molecule-1 (VCAM-1) in a transwell migration assay, suggesting involvement of Lnk in the regulation of cell mobility or cellular interaction in microenvironments. Transient inhibition of Lnk or Lnk-mediated pathways could be a potent approach to augment engraftment of HSCs/HPCs without obvious side effects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Chateauvieux, J.-L. Ichante, B. Delorme, V. Frouin, G. Pietu, A. Langonne, N. Gallay, L. Sensebe, M. T. Martin, K. A. Moore, et al. Molecular profile of mouse stromal mesenchymal stem cells Physiol Genomics, April 24, 2007; 29(2): 128 - 138. [Abstract] [Full Text] [PDF] J. Seita, H. Ema, J. Ooehara, S. Yamazaki, Y. Tadokoro, A. Yamasaki, K. Eto, S. Takaki, K. Takatsu, and H. Nakauchi Lnk negatively regulates self-renewal of hematopoietic stem cells by modifying thrombopoietin-mediated signal transduction PNAS, February 13, 2007; 104(7): 2349 - 2354. [Abstract] [Full Text] [PDF]

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