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Differential regulation of OCT4 targets facilitates reacquisition of pluripotency

Author

Listed:
  • Sudhir Thakurela

    (Harvard University
    Broad Institute of MIT and Harvard)

  • Camille Sindhu

    (Harvard University)

  • Evgeny Yurkovsky

    (Tel Aviv University
    Tel Aviv University)

  • Christina Riemenschneider

    (Max Planck Institute for Molecular Genetics)

  • Zachary D. Smith

    (Harvard University
    Broad Institute of MIT and Harvard)

  • Iftach Nachman

    (Tel Aviv University)

  • Alexander Meissner

    (Harvard University
    Broad Institute of MIT and Harvard
    Max Planck Institute for Molecular Genetics)

Abstract

Ectopic transcription factor expression enables reprogramming of somatic cells to pluripotency, albeit with generally low efficiency. Despite steady progress in the field, the exact molecular mechanisms that coordinate this remarkable transition still remain largely elusive. To better characterize the final steps of pluripotency induction, we optimized an experimental system where pluripotent stem cells are differentiated for set intervals before being reintroduced to pluripotency-supporting conditions. Using this approach, we identify a transient period of high-efficiency reprogramming where ectopic transcription factors, but not serum/LIF alone, rapidly revert cells to pluripotency with near 100% efficiency. After this period, cells reprogram with somatic-like kinetics and efficiencies. We identify a set of OCT4 bound cis-regulatory elements that are dynamically regulated during this transient phase and appear central to facilitating reprogramming. Interestingly, these regions remain hypomethylated during in vitro and in vivo differentiation, which may allow them to act as primary targets of ectopically induced factors during somatic cell reprogramming.

Suggested Citation

  • Sudhir Thakurela & Camille Sindhu & Evgeny Yurkovsky & Christina Riemenschneider & Zachary D. Smith & Iftach Nachman & Alexander Meissner, 2019. "Differential regulation of OCT4 targets facilitates reacquisition of pluripotency," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11741-5
    DOI: 10.1038/s41467-019-11741-5
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