Abstract
The objective of this study was to employ genetically engineered IGF-II analogs to establish which receptor(s) mediate the stemness promoting actions of IGF-II on mouse subventricular zone neural precursors. Neural precursors from the subventricular zone were propagated in vitro in culture medium supplemented with IGF-II analogs. Cell growth and identity were analyzed using sphere generation and further analyzed by flow cytometry. F19A, an analog of IGF-II that does not bind the IGF-2R, stimulated an increase in the proportion of neural stem cells (NSCs) while decreasing the proportion of the later stage progenitors at a lower concentration than IGF-II. V43M, which binds to the IGF-2R with high affinity but which has low binding affinity to the IGF-1R and to the A isoform of the insulin receptor (IR-A) failed to promote NSC growth. The positive effects of F19A on NSC growth were unaltered by the addition of a functional blocking antibody to the IGF-1R. Altogether, these data lead to the conclusion that IGF-II promotes stemness of NSCs via the IR-A and not through activation of either the IGF-1R or the IGF-2R.
Highlights
insulin-like growth factor (IGF)-II promotes neural stem cell (NSC) proliferation and self-renewal
A recent study suggested that IGF-2R promotes memory consolidation in vivo [18]; which is connected to the maintenance of hippocampal neurogenesis
Transcription Factor, Id2, Associated with Stemness, Is Induced by IGF-II—Because we observed an increase in the number of neurospheres grown in 4.4 nM insulin with IGF-II or F19A, we examined the expression of a group of transcription factor genes responsible for maintaining stemness
Summary
IGF-II promotes neural stem cell (NSC) proliferation and self-renewal. Results: IGF-II analogs are useful for elucidating the receptors responsible for NSC expansion. The objective of this study was to employ genetically engineered IGF-II analogs to establish which receptor(s) mediate the stemness promoting actions of IGF-II on mouse subventricular zone neural precursors. F19A, an analog of IGF-II that does not bind the IGF-2R, stimulated an increase in the proportion of neural stem cells (NSCs) while decreasing the proportion of the later stage progenitors at a lower concentration than IGF-II. The positive effects of F19A on NSC growth were unaltered by the addition of a functional blocking antibody to the IGF-1R. These data lead to the conclusion that IGF-II promotes stemness of NSCs via the IR-A and not through activation of either the IGF-1R or the IGF-2R
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