Journal article

GSK3 inhibition, but not epigenetic remodeling, mediates efficient derivation of germline embryonic stem cells from nonobese diabetic mice

Jun Liu, Michelle P Ashton, Moira K O'Bryan, Thomas C Brodnicki, Paul J Verma



The nonobese diabetic (NOD) mouse strain is a predominant animal model of type 1 diabetes. However, this mouse strain is considered to be non-permissive for embryonic stem cell (ESC) derivation using conventional methods. We examined small molecule inhibition of glycogen synthase kinase 3 (GSK3) to block spontaneous cell differentiation and promote pluripotency persistence. Here we show a single pharmacological GSK3 inhibitor, 6-bromoindirubin-3'-oxime (BIO), in combination with leukemia inhibition factor (LIF), promoted generation of stable NOD ESC lines at >80% efficiency. Significantly, expansion of the established NOD ESC lines no longer required treatment with BIO. These NOD ESC lines c..

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Awarded by Australian NHMRC

Awarded by NIH/NIDDK

Funding Acknowledgements

The authors thank Susan Chapman from the Australian Phenomics Network for blastocyst microinjection and embryo transfers, and Stephanie Meehan from the Monash Medical Centre Animal Facility for mouse husbandry and diabetes testing. The work was funded in part by financial support from the Australian Phenomics Network (APN), which is an initiative of the Australian Federal Government's National Collaborative Research Infrastructure Strategy, the Australian NHMRC (1029231), and the NIH/NIDDK (R01DK062882). This work was supported by the Victorian Government's Operational Infrastructure Support Program.