Cyclosporine a-mediated il-6 expression promotes neural induction in pluripotent stem cells

Ashwini, Ashwathnarayan and Naganur, Sushma S and Smitha, Bhaskar and Sheshadri, Preethi and Prasanna, Jyothi and Kumar, Anujith (2016) Cyclosporine a-mediated il-6 expression promotes neural induction in pluripotent stem cells. Molecular Neurobiology, 53 (8). pp. 1-15. ISSN 0893-7648

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Abstract

Differentiation of pluripotent stem cells (PSCs) to neural lineages has gathered huge attention in both basic research and regenerative medicine. The major hurdle lies in the efficiency of differentiation and identification of small molecules that facilitate neurogenesis would partly circumvent this limitation. The small molecule Cyclosporine A (CsA), a commonly used immunosuppressive drug, has been shown to enhance in vivo neurogenesis. To extend the information to in vitro neurogenesis, we examined the effect of CsA on neural differentiation of PSCs. We found CsA to increase the expression of neural progenitor genes during early neural differentiation. Gene silencing approach revealed CsA-mediated neural induction to be dependent on blocking the Ca2+-activated phosphatase calcineurin (Cn) signaling. Similar observation with FK506, an independent inhibitor of Cn, further strengthened the necessity of blocking Cn for enhanced neurogenesis. Surprisingly, mechanistic insight revealed Cninhibition dependent upregulation of IL-6 protein to be necessary for CsA-mediated neurogenesis. Together, these findings provide a comprehensive understanding of the role of CsA in neurogenesis, thus suggesting a method for obtaining large numbers of neural progenitors from PSCs for possible transplantation.

Item Type: Article
Uncontrolled Keywords: Neural differentiation ; miPSCs ; Cyclosporine A ; Calcineurin-NFAT pathway ; FK506.
Subjects: Regenerative Medicine > MIRM Bangalore
Depositing User: MCON Library
Date Deposited: 10 Nov 2017 09:09
Last Modified: 10 Nov 2017 09:09
URI: http://eprints.manipal.edu/id/eprint/149933

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