Abstract
SummaryMicroRNAs (miRNAs) are important regulators of reprogramming of somatic cells into induced pluripotent stem cells (iPSCs); however, it is unclear whether miRNAs are required for reprogramming and whether miRNA activity as a whole facilitates reprogramming. Here we report on successful reprogramming of mouse fibroblasts and neural stem cells (NSCs) lacking Dgcr8, a factor required for the biogenesis of canonical miRNAs, by Yamanaka factors, albeit at decreased efficiencies. Though iPSCs derived from Dgcr8-deficient mouse fibroblasts or NSCs were able to self-renew and expressed pluripotency-associated markers, they exhibited poor differentiation potential into mature somatic tissues, similar to Dgcr8−/− embryonic stem cells. The differentiation defects could be rescued with expression of DGCR8 cDNA. Our data demonstrate that while miRNA activity as a whole facilitates reprogramming, canonical miRNA may be dispensable in the derivation of iPSCs.
Highlights
MicroRNAs are short, endogenous, non-coding RNAs that repress gene expression post-transcriptionally by destabilizing and/or repressing translation of target mRNAs
MicroRNAs are important regulators of reprogramming of somatic cells into induced pluripotent stem cells; it is unclear whether miRNAs are required for reprogramming and whether miRNA activity as a whole facilitates reprogramming
We report on successful reprogramming of mouse fibroblasts and neural stem cells (NSCs) lacking Dgcr8, a factor required for the biogenesis of canonical miRNAs, by Yamanaka factors, albeit at decreased efficiencies
Summary
MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that repress gene expression post-transcriptionally by destabilizing and/or repressing translation of target mRNAs. Together with the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC) (Takahashi and Yamanaka, 2006), co-expression of the miRNA cluster 302/367 or 106a/363; members of the miR-302, miR-294, or miR-181 family; or miR-93 and miR-106b greatly enhance iPSC derivation efficiency (Judson et al, 2013; Li et al, 2011; Liao et al, 2011; Lin et al, 2011; Subramanyam et al, 2011). Expression of the miR-302/367 cluster or miR-200c, miR-302, and miR-369 without the Yamanaka factors is sufficient to reprogram human and mouse fibroblasts (Anokye-Danso et al, 2011; Miyoshi et al, 2011). How these miRNAs promote reprogramming is only partially understood. Several mechanisms have been proposed, such as acceleration of mesenchymal to epithelial transition and antagonism of the activities of let-7 family miRNAs, MBD2, NR2F2, and/or other reprogramming suppressors (Hu et al, 2013; Judson et al, 2013; Lee et al, 2013; Liao et al, 2011; Melton et al, 2010)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
