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CRISPR activation enables high-fidelity reprogramming into human pluripotent stem cells

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dc.contributor.author Sokka, Joonas
dc.contributor.author Yoshihara, Masahito
dc.contributor.author Kvist, Jouni
dc.contributor.author Laiho, Laura
dc.contributor.author Warren, Andrew
dc.contributor.author Stadelmann, Christian
dc.contributor.author Jouhilahti, Eeva-Mari
dc.contributor.author Kilpinen, Helena
dc.contributor.author Balboa, Diego
dc.contributor.author Katayama, Shintaro
dc.contributor.author Kyttälä, Aija
dc.contributor.author Kere, Juha
dc.contributor.author Otonkoski, Timo
dc.contributor.author Weltner, Jere
dc.contributor.author Trokovic, Ras
dc.date.accessioned 2022-04-20T06:30:37Z
dc.date.available 2022-04-20T06:30:37Z
dc.date.issued 2022
dc.identifier.citation Sokka J, Yoshihara M, Kvist J, Laiho L, Warren A, Stadelmann C, Jouhilahti EM, Kilpinen H, Balboa D, Katayama S, Kyttälä A, Kere J, Otonkoski T, Weltner J, Trokovic R. CRISPR activation enables high-fidelity reprogramming into human pluripotent stem cells. Stem Cell Reports. 2022 Feb 8;17(2):413-26. DOI: 10.1016/j.stemcr.2021.12.017
dc.identifier.issn 2213-6711
dc.identifier.uri http://hdl.handle.net/10230/52856
dc.description.abstract Conventional reprogramming methods rely on the ectopic expression of transcription factors to reprogram somatic cells into induced pluripotent stem cells (iPSCs). The forced expression of transcription factors may lead to off-target gene activation and heterogeneous reprogramming, resulting in the emergence of alternative cell types and aberrant iPSCs. Activation of endogenous pluripotency factors by CRISPR activation (CRISPRa) can reduce this heterogeneity. Here, we describe a high-efficiency reprogramming of human somatic cells into iPSCs using optimized CRISPRa. Efficient reprogramming was dependent on the additional targeting of the embryo genome activation-enriched Alu-motif and the miR-302/367 locus. Single-cell transcriptome analysis revealed that the optimized CRISPRa reprogrammed cells more directly and specifically into the pluripotent state when compared to the conventional reprogramming method. These findings support the use of CRISPRa for high-quality pluripotent reprogramming of human cells.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Stem Cell Reports. 2022 Feb 8;17(2):413-26
dc.rights © 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title CRISPR activation enables high-fidelity reprogramming into human pluripotent stem cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2021.12.017
dc.subject.keyword CRISPRa
dc.subject.keyword EEA
dc.subject.keyword LCL
dc.subject.keyword Human
dc.subject.keyword iPSC
dc.subject.keyword microRNA
dc.subject.keyword mir-302/367
dc.subject.keyword Reprogramming
dc.subject.keyword Single-cell RNA sequencing
dc.subject.keyword Transcriptomics
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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