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 journalArticle

7 Citations (Scopus)

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

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Stem cells
Mesenchymal Stromal Cells
stem cells
Down-Regulation
Neuroepithelial Cells
Proteins
proteins
Glycogen Synthase Kinase 3
Stem Cells
Tumors
ras GTPase-Activating Proteins
GTPase-activating proteins
neoplasms
neurogenesis
Cell Aging
Neurogenesis
Cell proliferation
small interfering RNA
Small Interfering RNA
Neurons

ASJC Scopus subject areas

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

Cite this

Downregulation of DAB2IP Promotes Mesenchymal-To-Neuroepithelial Transition and Neuronal Differentiation of Human Mesenchymal Stem Cells. / Chang, Sunny Li Yun; Chou, Ruey Hwang; Zeng, Hong Jie; Lin, Yu Hsuan; Chiu, Tai Yu; Yang, De Ming; Hung, Shih Chieh; Lai, Chih Ho; Hsieh, Jer Tsong; Shyu, Woei Cherng; Yu, Yung Luen.

In: PLoS One, Vol. 8, No. 9, e75884, 20.09.2013.

Research output: Contribution to journalArticle

Chang, SLY, Chou, RH, Zeng, HJ, Lin, YH, Chiu, TY, Yang, DM, Hung, SC, Lai, CH, Hsieh, JT, Shyu, WC & Yu, YL 2013, 'Downregulation of DAB2IP Promotes Mesenchymal-To-Neuroepithelial Transition and Neuronal Differentiation of Human Mesenchymal Stem Cells', PLoS One, vol. 8, no. 9, e75884. https://doi.org/10.1371/journal.pone.0075884
Chang, Sunny Li Yun ; Chou, Ruey Hwang ; Zeng, Hong Jie ; Lin, Yu Hsuan ; Chiu, Tai Yu ; Yang, De Ming ; Hung, Shih Chieh ; Lai, Chih Ho ; Hsieh, Jer Tsong ; Shyu, Woei Cherng ; Yu, Yung Luen. / Downregulation of DAB2IP Promotes Mesenchymal-To-Neuroepithelial Transition and Neuronal Differentiation of Human Mesenchymal Stem Cells. In: PLoS One. 2013 ; Vol. 8, No. 9.
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