Human pluripotent reprogramming with CRISPR activators.

Nat Commun

Research Programs Unit, Molecular Neurology and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.

Published: July 2018

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035213PMC
http://dx.doi.org/10.1038/s41467-018-05067-xDOI Listing

Publication Analysis

Top Keywords

cellular reprogramming
8
targeting endogenous
8
ipscs crispra
8
reprogramming
5
human pluripotent
4
pluripotent reprogramming
4
reprogramming crispr
4
crispr activators
4
activators crispr-cas9-based
4
crispr-cas9-based gene
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!