title: Canonical MicroRNA Activity Facilitates but May Be Dispensable for Transcription Factor-Mediated Reprogramming.
abstract: MicroRNAs (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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Stem Cell Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Sloan-Kettering Institute, Cell and Developmental Biology Program, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Skamagki
authors.affiliation: Cancer Biology and Genetics Program, Center for Cell Engineering, Center for Stem Cell Biology, Sloan-Kettering Institute, Cell and Developmental Biology Program, Weill Medical College of Cornell University, New York, NY 10065, USA. Electronic address: kimk@mskcc.org.
authors.forename: Kitai
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Genetics, Stem Cell Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: ruizhao@uab.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins