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Letters to Nature

Nature 430, 350-356 (15 July 2004) | doi:10.1038/nature02604; Received 15 January 2004; Accepted 23 April 2004

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Cell fusion-independent differentiation of neural stem cells to the endothelial lineage

Andrew E. Wurmser1, Kinichi Nakashima1,2, Robert G. Summers1, Nicolas Toni1, Kevin A. D'Amour1, Dieter C. Lie1 & Fred H. Gage1

  1. The Salk Institute, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
  2. Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan

Correspondence to: Fred H. Gage1 Email: gage@salk.edu

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Somatic stem cells have been claimed to possess an unexpectedly broad differentiation potential (referred to here as plasticity) that could be induced by exposing stem cells to the extracellular developmental signals of other lineages in mixed-cell cultures1, 2, 3, 4, 5, 6. Recently, this and other experimental evidence supporting the existence of stem-cell plasticity have been refuted because stem cells have been shown to adopt the functional features of other lineages by means of cell-fusion-mediated acquisition of lineage-specific determinants (chromosomal DNA) rather than by signal-mediated differentiation1, 2, 5, 7, 8. In this study we co-cultured mouse neural stem cells (NSCs), which are committed to become neurons and glial cells9, 10, with human endothelial cells, which form the lining of blood vessels11. We show that in the presence of endothelial cells six per cent of the NSC population converted to cells that did not express neuronal or glial markers, but instead showed the stable expression of multiple endothelial markers and the capacity to form capillary networks. This was surprising because NSCs and endothelial cells are believed to develop from the ectoderm and mesoderm, respectively. Experiments in which endothelial cells were killed by fixation before co-culture with live NSCs (to prevent cell fusion) and karyotyping analyses, revealed that NSCs had differentiated into endothelial-like cells independently of cell fusion. We conclude that stem-cell plasticity is a true characteristic of NSCs and that the conversion of NSCs to unanticipated cell types can be accomplished without cell fusion.