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Human pluripotent reprogramming with CRISPR activators

Author

Listed:
  • Jere Weltner

    (University of Helsinki)

  • Diego Balboa

    (University of Helsinki)

  • Shintaro Katayama

    (Karolinska Institutet)

  • Maxim Bespalov

    (University of Helsinki)

  • Kaarel Krjutškov

    (Karolinska Institutet
    Competence Centre on Health Technologies)

  • Eeva-Mari Jouhilahti

    (University of Helsinki)

  • Ras Trokovic

    (University of Helsinki)

  • Juha Kere

    (University of Helsinki
    Karolinska Institutet
    King’s College London
    Folkhälsan Institute of Genetics)

  • Timo Otonkoski

    (University of Helsinki
    University of Helsinki)

Abstract

CRISPR-Cas9-based gene activation (CRISPRa) is an attractive tool for cellular reprogramming applications due to its high multiplexing capacity and direct targeting of endogenous loci. Here we present the reprogramming of primary human skin fibroblasts into induced pluripotent stem cells (iPSCs) using CRISPRa, targeting endogenous OCT4, SOX2, KLF4, MYC, and LIN28A promoters. The low basal reprogramming efficiency can be improved by an order of magnitude by additionally targeting a conserved Alu-motif enriched near genes involved in embryo genome activation (EEA-motif). This effect is mediated in part by more efficient activation of NANOG and REX1. These data demonstrate that human somatic cells can be reprogrammed into iPSCs using only CRISPRa. Furthermore, the results unravel the involvement of EEA-motif-associated mechanisms in cellular reprogramming.

Suggested Citation

  • Jere Weltner & Diego Balboa & Shintaro Katayama & Maxim Bespalov & Kaarel Krjutškov & Eeva-Mari Jouhilahti & Ras Trokovic & Juha Kere & Timo Otonkoski, 2018. "Human pluripotent reprogramming with CRISPR activators," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05067-x
    DOI: 10.1038/s41467-018-05067-x
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    Cited by:

    1. Claire Vinel & Gabriel Rosser & Loredana Guglielmi & Myrianni Constantinou & Nicola Pomella & Xinyu Zhang & James R. Boot & Tania A. Jones & Thomas O. Millner & Anaelle A. Dumas & Vardhman Rakyan & Je, 2021. "Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-20, December.

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