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https://www.arca.fiocruz.br/handle/icict/20681
POLYSOME PROFILING SHOWS EXTENSIVE POSTTRANSCRIPTIONAL REGULATION DURING HUMAN ADIPOCYTE STEM CELL DIFFERENTIATION INTO ADIPOCYTES
Author
Spangenberg, Lucia
Shigunov, Patrícia
Abud, Ana Paula Ressetti
Cofré, Axel Helmut Rulf
Stimamiglio, Marco Augusto
Kuligovski, Crisciele
Zych, Jaiesa
Schittini, Andressa V.
Costa, Alexandre Dias Tavares
Rebelatto, Carmen Lúcia Kuniyoshi
Brofman, Paulo Roberto Slud
Goldenberg, Samuel
Correa, Alejandro
Naya, Hugo
Dallagiovanna, Bruno
Shigunov, Patrícia
Abud, Ana Paula Ressetti
Cofré, Axel Helmut Rulf
Stimamiglio, Marco Augusto
Kuligovski, Crisciele
Zych, Jaiesa
Schittini, Andressa V.
Costa, Alexandre Dias Tavares
Rebelatto, Carmen Lúcia Kuniyoshi
Brofman, Paulo Roberto Slud
Goldenberg, Samuel
Correa, Alejandro
Naya, Hugo
Dallagiovanna, Bruno
Affilliation
Institut Pasteur Montevideo. Unidad de Bioinformática. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Pontifícia Universidade Católica do Paraná. Núcleo de Tecnologia Celular. Curitiba, PR, Brasil.
Pontifícia Universidade Católica do Paraná. Núcleo de Tecnologia Celular. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Montevideo. Unidad de Bioinformática. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Pontifícia Universidade Católica do Paraná. Núcleo de Tecnologia Celular. Curitiba, PR, Brasil.
Pontifícia Universidade Católica do Paraná. Núcleo de Tecnologia Celular. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Montevideo. Unidad de Bioinformática. Montevideo, Uruguay.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
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.
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