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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Nat+Commun
2018 ; 9
(1
): 2643
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Human pluripotent reprogramming with CRISPR activators
#MMPMID29980666
Weltner J
; Balboa D
; Katayama S
; Bespalov M
; Krjut?kov K
; Jouhilahti EM
; Trokovic R
; Kere J
; Otonkoski T
Nat Commun
2018[Jul]; 9
(1
): 2643
PMID29980666
show ga
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.
|Alu Elements/genetics
[MESH]
|Base Sequence
[MESH]
|CRISPR-Associated Protein 9/*metabolism
[MESH]
|Cellular Reprogramming/*genetics
[MESH]
|Clustered Regularly Interspaced Short Palindromic Repeats/*genetics
[MESH]