Olig2-induced Neural Stem Cell Differentiation Involves Downregulation of Wnt Signaling and Induction of Dickkopf-1 Expression

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Dec 19

PMID 19093005

Citations 23

Authors

Sung-Min Ahn

Kyunghee Byun

Deokhoon Kim

Kiyoung Lee

Jong Shin Yoo

Seung U Kim

Eek-Hoon Jho

Richard J Simpson

Bonghee Lee

Affiliations

Soon will be listed here.

Abstract

Understanding stem cell-differentiation at the molecular level is important for clinical applications of stem cells and for finding new therapeutic approaches in the context of cancer stem cells. To investigate genome-wide changes involved in differentiation, we have used immortalized neural stem cell (NSC) line (HB1.F3) and Olig2-induced NSC differentiation model (F3.Olig2). Using microarray analysis, we revealed that Olig2-induced NSC differentiation involves downregulation of Wnt pathway, which was further confirmed by TOPflash/FOPflash reporter assay, RT-PCR analysis, immunoblots, and immunocytochemistry. Furthermore, we found that Olig2-induced differentiation induces the expression of Dickkopf-1(Dkk1), a potent antagonist of Wnt signaling. Dkk1 treatment blocked Wnt signaling in HB1.F3 in a dosage-dependent manner, and induced differentiation into astrocytes, oligodendrocytes, and neurons. Our results support cancer stem cell hypothesis which implies that signaling pathway for self-renewal and proliferation of stem cells is maintained till the late stage of differentiation. In our proposed model, Dkk1 may play an important role in downregulating self-renewal and proliferation pathway of stem cells at the late stage of differentiation, and its failure may lead to carcinogenesis.

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