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Downregulation of DAB2IP promotes mesenchymal-to-neuroepithelial transition and neuronal differentiation of human mesenchymal stem cells.


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 (GSK3?) 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 GSK3? 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.

SUBMITTER: Chang SL 

PROVIDER: S-EPMC3779184 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Downregulation of DAB2IP promotes mesenchymal-to-neuroepithelial transition and neuronal differentiation of human mesenchymal stem cells.

Chang Sunny Li-Yun SL   Chou Ruey-Hwang RH   Zeng Hong-Jie HJ   Lin Yu-Hsuan YH   Chiu Tai-Yu TY   Yang De-Ming DM   Hung Shih-Chieh SC   Lai Chih-Ho CH   Hsieh Jer-Tsong JT   Shyu Woei-Cherng WC   Yu Yung-Luen YL  

PloS one 20130920 9


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  ...[more]

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