Human pluripotent reprogramming with CRISPR activators
Jere Weltner (),
Diego Balboa,
Shintaro Katayama,
Maxim Bespalov,
Kaarel Krjutškov,
Eeva-Mari Jouhilahti,
Ras Trokovic,
Juha Kere () and
Timo Otonkoski ()
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Jere Weltner: University of Helsinki
Diego Balboa: University of Helsinki
Shintaro Katayama: Karolinska Institutet
Maxim Bespalov: University of Helsinki
Kaarel Krjutškov: Karolinska Institutet
Eeva-Mari Jouhilahti: University of Helsinki
Ras Trokovic: University of Helsinki
Juha Kere: University of Helsinki
Timo Otonkoski: University of Helsinki
Nature Communications, 2018, vol. 9, issue 1, 1-12
Abstract:
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.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05067-x
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DOI: 10.1038/s41467-018-05067-x
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