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

• Published in: Nature Vol. 430; no. 6997; pp. 350 - 356
• Main Authors: Gage, Fred H, Wurmser, Andrew E, Nakashima, Kinichi, Summers, Robert G, Toni, Nicolas, D'Amour, Kevin A, Lie, Dieter C
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 15-07-2004
• Subjects: Animals; Antigens, CD; Biomarkers - analysis; Capillaries - cytology; Capillaries - metabolism; CD146 Antigen; Cell Differentiation; Cell Fusion; Cell Lineage; Cells; Cells, Cultured; Cellular biology; Clone Cells - cytology; Clone Cells - metabolism; Coculture Techniques; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Humans; Karyotyping; Membrane Glycoproteins - metabolism; Mice; Neural Cell Adhesion Molecules; Neurons; Neurons - cytology; Neurons - metabolism; Plasticity; Stem cells; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02604

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 cultures. 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 differentiation. In this study we co-cultured mouse neural stem cells (NSCs), which are committed to become neurons and glial cells, with human endothelial cells, which form the lining of blood vessels. 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.