Embryonic stem cell-specific microRNAs promote induced pluripotency

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This paper reports my first exploration into the use of microRNAs to induce transitions in cells state. Using the Yamanaka-strategy, I asked whether miRNAs that were highly and specifically expressed in ESCs could aid in the reprogramming of differentiated cells into iPSCs. We found that miRNAs from the miR-302 and miR-290 clusters could replace cMyc in the Oct4/Sox2/Klf4/cMyc cocktail of transcription factors and induce full de-differentiation of mouse fibroblasts. Interestingly, the microRNAs also conferred more specificity to the transition as compared to cMyc, and did not result in partially reprogrammed colonies or transformed cells.

miR-294 and miR-302 increase the sensitivity of fibroblasts to OSK-induced somatic cell reprogramming. Point mutations to the seed sequence abrogate this effect. Increasing doses of miR-294 bring the efficiency to Myc-like levels.

Publications

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CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation

Stem Cell Reports 2015

Noelle E Huskey, Tingxia Guo, Kimberley J Evason, Olga Momcilovic, David Pardo, Katelyn J Creasman, Robert L Judson, Robert Blelloch, Sco...

Two miRNA Clusters Reveal Alternative Paths in Late-Stage Reprogramming

Cell Stem Cell 2014

Ronald J Parchem, Julia Ye, Robert L Judson, Marie F Larussa,Raga Krishnakumar, Amy Blelloch, Michael C Oldham, Robert Blelloch

MicroRNA-based discovery of barriers to dedifferentiation of fibroblasts to pluripotent stem cells

Nature Structural & Molecular Biology 2013

Robert L Judson, Tobias S Greve, Ronald J Parchem, Robert Blelloch

microRNA Control of Mouse and Human Pluripotent Stem Cell Behavior

Annual Review of Cell and Developmental Biology 2013

Tobias S Greve, Robert L Judson, Robert Blelloch

Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells

Nature Biotechnology 2011

Deepa Subramanyam, Samy Lamouille, Robert L Judson, Jason Y Liu, Nathan Bucay, Rik Derynck, Robert Blelloch

miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma

Nature Medicine 2010

Alexander Swarbrick, Susan L Woods, Alexander Shaw, Asha Balakrishnan, Yuwei Phua, Akira Nguyen, Yvan Chanthery, Lionel Lim, Lesley J Ash...

Opposing microRNA families regulate self-renewal in mouse embryonic stem cells

Nature 2010

Collin Melton, Robert L Judson, Robert Blelloch

Embryonic stem cell-specific microRNAs promote induced pluripotency

Nature Biotechnology 2009

Robert L Judson, Joshua E Babiarz, Monica Venere, Robert Blelloch

The GP(Y/F) domain of TF1 integrase multimerizes when present in a fragment, and substitutions in this domain reduce enzymatic activity of the full-length protein

Journal of Biological Chemistry 2008

Hirotaka Ebina, Atreyi Ghatak Chatterjee, Robert L Judson, Henry L Levin

The self primer of the long terminal repeat retrotransposon Tf1 is not removed during reverse transcription.

Journal of Virology 2006

Angela Atwood-Moore, Kenneth Yan, Robert L Judson, Henry L Levin

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