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Originally published in Science Express on 5 September 2002
Science 27 September 2002:
Vol. 297. no. 5590, pp. 2256 - 2259
DOI: 10.1126/science.1074807
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Reports

Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells

Amy J. Wagers,* Richard I. Sherwood, Julie L. Christensen, Irving L. Weissman

To rigorously test the in vivo cell fate specificity of bone marrow (BM) hematopoietic stem cells (HSCs), we generated chimeric animals by transplantation of a single green fluorescent protein (GFP)-marked HSC into lethally irradiated nontransgenic recipients. Single HSCs robustly reconstituted peripheral blood leukocytes in these animals, but did not contribute appreciably to nonhematopoietic tissues, including brain, kidney, gut, liver, and muscle. Similarly, in GFP+:GFP- parabiotic mice, we found substantial chimerism of hematopoietic but not nonhematopoietic cells. These data indicate that "transdifferentiation" of circulating HSCs and/or their progeny is an extremely rare event, if it occurs at all.

Department of Pathology and Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
*   To whom correspondence should be addressed. E-mail: awagers{at}stanford.edu

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Proceedings of the ATS 3, 373-376
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Bone Marrow Lacks a Transplantable Progenitor for Smooth Muscle Type {alpha}-Actin-Expressing Cells.
T. Yokota, Y. Kawakami, Y. Nagai, J.-x. Ma, J.-Y. Tsai, P. W. Kincade, and S. Sato (2006)
Stem Cells 24, 13-22
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Human umbilical cord blood-derived cells differentiate into hepatocyte-like cells in the Fas-mediated liver injury model.
K. Nonome, X.-K. Li, T. Takahara, Y. Kitazawa, N. Funeshima, Y. Yata, F. Xue, M. Kanayama, E. Shinno, C. Kuwae, et al. (2005)
Am J Physiol Gastrointest Liver Physiol 289, G1091-G1099
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Novel Autologous Cell Therapy in Ischemic Limb Disease Through Growth Factor Secretion by Cultured Adipose Tissue-Derived Stromal Cells.
H. Nakagami, K. Maeda, R. Morishita, S. Iguchi, T. Nishikawa, Y. Takami, Y. Kikuchi, Y. Saito, K. Tamai, T. Ogihara, et al. (2005)
Arterioscler. Thromb. Vasc. Biol. 25, 2542-2547
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Predominant fusion of bone marrow-derived cardiomyocytes.
J. Andrade, J. T. Lam, M. Zamora, C. Huang, D. Franco, N. Sevilla, P. J. Gruber, J. T. Lu, and P. Ruiz-Lozano (2005)
Cardiovasc Res 68, 387-393
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Heterogeneity of engrafted bone-lining cells after systemic and local transplantation.
L. Wang, Y. Liu, Z. Kalajzic, X. Jiang, and D. W. Rowe (2005)
Blood 106, 3650-3657
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Mobilization of Bone Marrow-Derived Cells Enhances the Angiogenic Response to Hypoxia Without Transdifferentiation Into Endothelial Cells.
T. J. O'Neill IV, B. R. Wamhoff, G. K. Owens, and T. C. Skalak (2005)
Circ. Res. 97, 1027-1035
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IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors.
A. Sacco, R. Doyonnas, M. A. LaBarge, M. M. Hammer, P. Kraft, and H. M. Blau (2005)
J. Cell Biol. 171, 483-492
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From The Cover: Long-term renewal of hair follicles from clonogenic multipotent stem cells.
S. Claudinot, M. Nicolas, H. Oshima, A. Rochat, and Y. Barrandon (2005)
PNAS 102, 14677-14682
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Cardiac Stem Cells and Mechanisms of Myocardial Regeneration.
A. Leri, J. Kajstura, and P. Anversa (2005)
Physiol Rev 85, 1373-1416
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Failure of Bone Marrow to Reconstitute Lung Epithelium.
D. N. Kotton, A. J. Fabian, and R. C. Mulligan (2005)
Am. J. Respir. Cell Mol. Biol. 33, 328-334
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Evidence that Bone Marrow Cells Do Not Contribute to the Alveolar Epithelium.
J. C. Chang, R. Summer, X. Sun, K. Fitzsimmons, and A. Fine (2005)
Am. J. Respir. Cell Mol. Biol. 33, 335-342
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Glial grafting for demyelinating disease.
V Tepavcevic and W.F Blakemore (2005)
Phil Trans R Soc B 360, 1775-1795
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Stem Cell Research: Paths to Cancer Therapies and Regenerative Medicine.
I. Weissman (2005)
JAMA 294, 1359-1366
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Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading.
H. Makui, R. J. Soares, W. Jiang, M. Constante, and M. M. Santos (2005)
Blood 106, 2189-2195
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Stem Cell Approaches for the Treatment of Renal Failure.
J. C. Brodie and H. D. Humes (2005)
Pharmacol. Rev. 57, 299-313
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