title: The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming.
abstract: Long intergenic noncoding RNAs (lincRNAs) are derived from thousands of loci in mammalian genomes and are frequently enriched in transposable elements (TEs). Although families of TE-derived lincRNAs have recently been implicated in the regulation of pluripotency, little is known of the specific functions of individual family members. Here we characterize three new individual TE-derived human lincRNAs, human pluripotency-associated transcripts 2, 3 and 5 (HPAT2, HPAT3 and HPAT5). Loss-of-function experiments indicate that HPAT2, HPAT3 and HPAT5 function in preimplantation embryo development to modulate the acquisition of pluripotency and the formation of the inner cell mass. CRISPR-mediated disruption of the genes for these lincRNAs in pluripotent stem cells, followed by whole-transcriptome analysis, identifies HPAT5 as a key component of the pluripotency network. Protein binding and reporter-based assays further demonstrate that HPAT5 interacts with the let-7 microRNA family. Our results indicate that unique individual members of large primate-specific lincRNA families modulate gene expression during development and differentiation to reinforce cell fate.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Durruthy-Durruthy
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sebastiano
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Wossidlo
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Cepeda
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Jun
authors.identifier: http://orcid.org/0000-0002-1926-1759
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Grow
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Davila
authors.affiliation: Department of Pathology, Stanford University, Stanford, California, USA.
authors.forename: Moritz
authors.initials: M
authors.lastname: Mall
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, USA.
authors.forename: Wing H
authors.initials: WH
authors.lastname: Wong
authors.affiliation: Department of Chemical and Systems Biology, Stanford University, Stanford, California, USA.|Department of Developmental Biology, Stanford University, Stanford, California, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.affiliation: Department of Statistics, Stanford University, Stanford, California, USA.
authors.forename: Kin Fai
authors.initials: KF
authors.lastname: Au
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Genetics, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Stanford University, Stanford, California, USA.
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D011323:Primates / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D059010:Single-Cell Analysis
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; C487931:mirnlet7 microRNA, human