title: Polysome profiling shows extensive posttranscriptional regulation during human adipocyte stem cell differentiation into adipocytes.
abstract: Adipocyte stem cells (hASCs) can proliferate and self-renew and, due to their multipotent nature, they can differentiate into several tissue-specific lineages, making them ideal candidates for use in cell therapy. Most attempts to determine the mRNA profile of self-renewing or differentiating stem cells have made use of total RNA for gene expression analysis. Several lines of evidence suggest that self-renewal and differentiation are also dependent on the control of protein synthesis by posttranscriptional mechanisms. We used adipogenic differentiation as a model, to investigate the extent to which posttranscriptional regulation controlled gene expression in hASCs. We focused on the initial steps of differentiation and isolated both the total mRNA fraction and the subpopulation of mRNAs associated with translating ribosomes. We observed that adipogenesis is committed in the first days of induction and three days appears as the minimum time of induction necessary for efficient differentiation. RNA-seq analysis showed that a significant percentage of regulated mRNAs were posttranscriptionally controlled. Part of this regulation involves massive changes in transcript untranslated regions (UTR) length, with differential extension/reduction of the 3'UTR after induction. A slight correlation can be observed between the expression levels of differentially expressed genes and the 3'UTR length. When we considered association to polysomes, this correlation values increased. Changes in the half lives were related to the extension of the 3'UTR, with longer UTRs mainly stabilizing the transcripts. Thus, changes in the length of these extensions may be associated with changes in the ability to associate with polysomes or in half-life.
authors.affiliation: Unidad de Bioinformática, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors.forename: Lucia
authors.initials: L
authors.lastname: Spangenberg
authors.forename: Patricia
authors.initials: P
authors.lastname: Shigunov
authors.forename: Ana Paula R
authors.initials: AP
authors.lastname: Abud
authors.forename: Axel R
authors.initials: AR
authors.lastname: Cofré
authors.forename: Marco A
authors.initials: MA
authors.lastname: Stimamiglio
authors.forename: Crisciele
authors.initials: C
authors.lastname: Kuligovski
authors.forename: Jaiesa
authors.initials: J
authors.lastname: Zych
authors.forename: Andressa V
authors.initials: AV
authors.lastname: Schittini
authors.forename: Alexandre Dias Tavares
authors.initials: AD
authors.lastname: Costa
authors.forename: Carmen K
authors.initials: CK
authors.lastname: Rebelatto
authors.forename: Paulo R S
authors.initials: PR
authors.lastname: Brofman
authors.forename: Samuel
authors.initials: S
authors.lastname: Goldenberg
authors.forename: Alejandro
authors.initials: A
authors.lastname: Correa
authors.forename: Hugo
authors.initials: H
authors.lastname: Naya
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallagiovanna
mesh_terms: D020413:3' Untranslated Regions; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; D005978:Glutathione