Myc increases self-renewal in neural progenitor cells through Miz-1.
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.
Kerosuo
Laura
L
Developmental Biology, Institute of Biomedicine, Haartmaninkatu 8, PO Box 63, 00014 University of Helsinki, Finland.
Piltti
Katja
K
Fox
Heli
H
Angers-Loustau
Alexandre
A
Häyry
Valtteri
V
Eilers
Martin
M
Sariola
Hannu
H
Wartiovaara
Kirmo
K
D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D005455:Fluorescent Antibody Technique; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D051741:Kruppel-Like Transcription Factors; D016271:Proto-Oncogene Proteins c-myc