Downregulation of DAB2IP Promotes Mesenchymal-To-Neuroepithelial Transition and Neuronal Differentiation of Human Mesenchymal Stem Cells

Sunny Li Yun Chang, Ruey Hwang Chou, Hong Jie Zeng, Yu Hsuan Lin, Tai Yu Chiu, De Ming Yang, Shih Chieh Hung, Chih Ho Lai, Jer Tsong Hsieh, Woei Cherng Shyu, Yung Luen Yu

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The DOC-2/DAB2 interactive protein (DAB2IP) is a new member of the Ras GTPase-activating protein family. Recent studies have shown that, in addition to its tumor suppressive role in various tumors, DAB2IP also plays an important role in regulating neuronal migration and positioning during brain development. In this study, we determined the roles of DAB2IP in the neuronal differentiation of human mesenchymal stem cells (hMSCs). We found that lentiviral short hairpin RNA (shRNA)-mediated knockdown of DAB2IP promoted the mesenchymal-to-neuroepithelial stem cell transition (MtNeST) and neuronal differentiation, which were accompanied by a reduction of cell proliferation but not apoptosis or cellular senescence. This suggests that DAB2IP plays an important role in the neuronal induction of hMSCs. Moreover, our finding that reduction of glycogen synthase kinase 3 beta (GSK3β) activity upon LiCl pretreatment inhibited both the MtNeST and production of MAP2-positive cells upon DAB2IP knockdown suggests that this transition is most likely mediated by regulation of the GSK3β signaling pathway. Our study demonstrates that DAB2IP participates in the first step of neuron induction of hMSCs, which implies a potentially important role for DAB2IP in the MtNeST during neurogenesis.

Original languageEnglish (US)
Article numbere75884
JournalPloS one
Volume8
Issue number9
DOIs
StatePublished - Sep 20 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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