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First published online 4 August 2004
doi: 10.1242/dev.01295

Development 131, 4287-4298 (2004)
Published by The Company of Biologists 2004
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Insulin acts as a myogenic differentiation signal for neural stem cells with multilineage differentiation potential

Mahmud Bani-Yaghoub1,*, Stephen E. Kendall2, Daniel P. Moore2, Stephen Bellum2, Rebecca A. Cowling2, George N. Nikopoulos2, Chris J. Kubu1,{dagger}, Calvin Vary3 and Joseph M. Verdi1,2,{ddagger}

1 The John P. Roberts Research Institute, 100 Perth Drive, London, ON, N6A 5K8, Canada
2 Center for Regenerative Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA
3 Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA

{ddagger} Author for correspondence (e-mail: verdij{at}mmc.org)

Accepted 8 June 2004

Reports of non-neural differentiation of neural stem cells (NSCs) have been challenged by alternative explanations for expanded differentiation potentials. In an attempt to demonstrate the plasticity of NSC, neurospheres were generated from single retrovirally labeled embryonic cortical precursors. In a defined serum-free insulin-containing media, 40% of the neurospheres contained both myogenic and neurogenic differentiated progeny. The number of NSCs displaying multilineage differentiation potential declines through gestation but does exist in the adult animal. In this system, insulin appears to function as a survival and dose-dependent myogenic differentiation signal for multilineage NSCs (MLNSC). MLNSC-derived cardiomyocytes contract synchronously, respond to sympathetic and parasympathetic stimulation, and regenerate injured heart tissues. These studies provide support for the hypothesis that MLNSCs exist throughout the lifetime of the animal, and potentially provide a population of stem cells for cell-based regenerative medicine strategies inside and outside of the nervous system.

Key words: Plasticity, Neural stem cells, Myogenesis




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