Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency

By Frederick Anokye-Danso, C. Trivedi, D. Juhr, Mudit Gupta, Zheng Cui, Ying Tian, Yuzhen Zhang, Wenli Yang, P. Gruber, J. Epstein and 1 more. Cell Stem Cell, 2011

1,247 citations recorded by the source corpus.

Transcription factor-based cellular reprogramming has opened the way to converting somatic cells to a pluripotent state, but has faced limitations resulting from the requirement for transcription factors and the relative inefficiency of the process. We show here that expression of the miR302/367 cluster rapidly and efficiently reprograms mouse and human somatic cells to an iPS state without a requirement for exogenous transcription factors. This miRNA-based reprogramming approach is two orders of magnitude more efficient than standard Oct4/Sox2/Klf4/Myc-mediated methods. Mouse and human miR302/367 iPS cells display similar characteristics to Oct4/Sox2/Klf4/Myc-iPS cells, including pluripotency marker expression, teratoma formation, and, for mouse cells, chimera contribution and germline contribution. We found that miR367 expression is required for miR302/367-mediated reprogramming and activates Oct4 gene expression, and that suppression of Hdac2 is also required. Thus, our data show that miRNA and Hdac-mediated pathways can co-operate in a powerful way to reprogram somatic cells to pluripotency.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/caf991661dda5a227e9d0fd728f171dd529fb97b

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In Molecular Biology

1. Chaomei Chen
2. A. Soufi
3. Greg Donahue
4. Meen Chul Kim
5. Rachael Dubin
6. M. Jansson
7. K. Zaret
8. A. Lund

Citations in the corpus

• MicroRNA and cancer (2012, background): “Interestingly, miRNA also play key roles in stem cells and stem cell differentiation (Heinrich and Dimmeler, 2012) and in induced pluripotency where a single miRNA cluster, miR302, was recently shown to be able to produce iPSC from both human and mouse fibroblasts (Anokye-Danso et al., 2011).”
• Emerging trends and new developments in regenerative medicine: a scientometric update (2000 – 2014) (2014, background): “[33] on a more efficient reprogramming approach than existing approaches to reprogram somatic cells to pluripotency.”
• Reprogramming of mouse and human cells to pluripotency using mature microRNAs. (2011, background): “Very recently, highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency was reported (Anokye-Danso et al., 2011), but using integrating viral vectors and not direct transfection of mature miRNAs.”
• Facilitators and Impediments of the Pluripotency Reprogramming Factors’ Initial Engagement with the Genome (2012, positive): “The Initial OSKM Regulatory Network Promotes Reprogramming and Apoptosis OSKM bind together at genes that promote reprogramming, including GLIS1 (Maekawa et al., 2011), the mir-302/367 cluster (Anokye-Danso et al., 2011), and genes for MET such as SNAI2 (Figures 2B and S3C).”