title: Identification of differentially expressed non-coding RNAs in embryonic stem cell neural differentiation.
abstract: Protein-coding genes, guiding differentiation of ES cells into neural cells, have extensively been studied in the past. However, for the class of ncRNAs only the involvement of some specific microRNAs (miRNAs) has been described. Thus, to characterize the entire small non-coding RNA (ncRNA) transcriptome, involved in the differentiation of mouse ES cells into neural cells, we have generated three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i.e. from pluripotent ES cells, neural progenitors and differentiated neural cells, respectively. By high-throughput sequencing and transcriptional profiling we identified several novel miRNAs to be involved in ES cell differentiation, as well as seven small nucleolar RNAs. In addition, expression of 7SL, 7SK and vault-2 RNAs was significantly up-regulated during ES cell differentiation. About half of ncRNA sequences from the three cDNA libraries mapped to intergenic or intragenic regions, designated as interRNAs and intraRNAs, respectively. Thereby, novel ncRNA candidates exhibited a predominant size of 18-30 nt, thus resembling miRNA species, but, with few exceptions, lacking canonical miRNA features. Additionally, these novel intraRNAs and interRNAs were not only found to be differentially expressed in stem-cell derivatives, but also in primary cultures of hippocampal neurons and astrocytes, strengthening their potential function in neural ES cell differentiation.
authors.affiliation: Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, Innrain 80/82, A-6020 Innsbruck, Austria.
authors.forename: Konstantinia
authors.initials: K
authors.lastname: Skreka
authors.forename: Simon
authors.initials: S
authors.lastname: Schafferer
authors.forename: Irina-Roxanna
authors.initials: IR
authors.lastname: Nat
authors.forename: Marek
authors.initials: M
authors.lastname: Zywicki
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salti
authors.forename: Galina
authors.initials: G
authors.lastname: Apostolova
authors.forename: Matthias
authors.initials: M
authors.lastname: Griehl
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rederstorff
authors.forename: Georg
authors.initials: G
authors.lastname: Dechant
authors.forename: Alexander
authors.initials: A
authors.lastname: Hüttenhofer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D015723:Gene Library; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D022661:RNA, Untranslated; D012261:Ribonucleoproteins