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First published online 11 November 2008
doi: 10.1242/jcs.024802

Journal of Cell Science 121, 3941-3950 (2008)
Published by The Company of Biologists 2008
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Research Article

Myc increases self-renewal in neural progenitor cells through Miz-1

Laura Kerosuo1, Katja Piltti1, Heli Fox1, Alexandre Angers-Loustau1, Valtteri Häyry1, Martin Eilers2, Hannu Sariola1,3 and Kirmo Wartiovaara1,*

1 Developmental Biology, Institute of Biomedicine, Haartmaninkatu 8, PO Box 63, 00014 University of Helsinki, Finland
2 Institute for Molecular Biology and Tumor Research (IMT), University of Marburg, Emil-Mannkopff-Str.2, 35033 Marburg, Germany
3 HUCH Laboratory Diagnostics, Helsinki University Central Hospital, Finland

* Author for correspondence (e-mail: kirmo.wartiovaara{at}helsinki.fi)

Accepted 29 August 2008

The mechanisms underlying the decision of a stem or progenitor cell to either self-renew or differentiate are incompletely understood. To address the role of Myc in this process, we expressed different forms of the proto-oncogene Myc in multipotent neural progenitor cells (NPCs) using retroviral transduction. Expression of Myc in neurospheres increased the proportion of self-renewing cells fivefold, and 1% of the Myc-overexpressing cells, but none of the control cells, retained self-renewal capacity even under differentiation-inducing conditions. A Myc mutant (MycV394D) deficient in binding to Miz-1, did not increase the percentage of self-renewing cells but was able to stimulate proliferation of NPCs as efficiently as wild-type Myc, indicating that these two cellular phenomena are regulated by at least partially different pathways. Our results suggest that Myc, through Miz-1, enhances self-renewal of NPCs and influences the way progenitor cells react to the environmental cues that normally dictate the cellular identity of tissues containing self-renewing cells.

Key words: Myc, Self-renewal, Miz-1, Neural progenitor, Stem cell, Oncogene






© The Company of Biologists Ltd 2008