Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation

Yong Hee Rhee, Sang Hoon Yi, Joo Yeon Kim, Mi Yoon Chang, A. Young Jo, Jinyoung Kim, Chang Hwan Park, Je Yoel Cho, Young Jin Choi, Woong Sun, Sang Hun Lee

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12 Citations (Scopus)

Abstract

The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders.

Original languageEnglish
Article number32025
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Aug 24

ASJC Scopus subject areas

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    Rhee, Y. H., Yi, S. H., Kim, J. Y., Chang, M. Y., Jo, A. Y., Kim, J., Park, C. H., Cho, J. Y., Choi, Y. J., Sun, W., & Lee, S. H. (2016). Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation. Scientific reports, 6, [32025]. https://doi.org/10.1038/srep32025