Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-018-05067-x
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Funding
- 3i Regeneration project [40395/13]
- Jane and Aatos Erkko Foundation
- Academy of Finland [297466, 312437]
- Sigrid Juselius Foundation
- Novo Nordisk Foundation
- Instrumentarium Science Foundation
- Doctoral Program in Biomedicine at University of Helsinki
- Knut and Alice Wallenberg Foundation [KAW2015.0096]
- SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) [b2014069]
- Mutation Analysis Core Facility (MAF) at the Karolinska University Hospital
- Bioinformatics and Expression Analysis core facility (BEA)
- Academy of Finland (AKA) [297466, 312437, 297466, 312437] Funding Source: Academy of Finland (AKA)
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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.
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