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.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.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.doi http://dx.doi.org/10.1016/j.stemcr.2021.12.017
• dc.identifier.issn 2213-6711
• dc.identifier.uri http://hdl.handle.net/10230/52856
• 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• 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.title CRISPR activation enables high-fidelity reprogramming into human pluripotent stem cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion