Human pluripotent reprogramming with CRISPR activators

Jere Weltner, Diego Balboa, Shintaro Katayama, Maxim Bespalov, Kaarel Krjutškov, Eeva Mari Jouhilahti, Ras Trokovic, Juha Kere, Timo Otonkoski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)
103 Downloads (Pure)

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.

Original languageEnglish
Article number2643
Pages (from-to)1-12
JournalNature Communications
Volume9
Issue number1
Early online date6 Jul 2018
DOIs
Publication statusPublished - 1 Dec 2018

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