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Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Kurian, Leo; Aguirre, Aitor; Sancho-Martinez, Ignacio; Benner, Christopher; Hishida, Tomoaki; Nguyen, Thai B; Reddy, Pradeep; Nivet, Emmanuel; Krause, Marie N; Nelles, David A; Esteban, Concepcion Rodriguez; Campistol, Josep M; Yeo, Gene W; Belmonte, Juan Carlos Izpisua.
  • Kurian L; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Aguirre A; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Sancho-Martinez I; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Benner C; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Hishida T; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Nguyen TB; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Reddy P; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Nivet E; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Krause MN; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Nelles DA; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Esteban CR; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Campistol JM; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Yeo GW; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
  • Belmonte JCI; Gene Expression Laboratory (L.K., A.A., I.S.-M., T.H., T.B.N., P.R., E.N., M.N.K., C.R.E., J.C.I.B.) and Integrative Genomics Core (C.B.), Salk Institute for Biological Studies, La Jolla, CA; University of California San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, Instit
Circulation ; 131(14): 1278-1290, 2015 Apr 07.
Article en En | MEDLINE | ID: mdl-25739401
ABSTRACT

BACKGROUND:

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators with important functions in development and disease. Here, we sought to identify and functionally characterize novel lncRNAs critical for vertebrate development. METHODS AND

RESULTS:

By relying on human pluripotent stem cell differentiation models, we investigated lncRNAs differentially regulated at key steps during human cardiovascular development with a special focus on vascular endothelial cells. RNA sequencing led to the generation of large data sets that serve as a gene expression roadmap highlighting gene expression changes during human pluripotent cell differentiation. Stage-specific analyses led to the identification of 3 previously uncharacterized lncRNAs, TERMINATOR, ALIEN, and PUNISHER, specifically expressed in undifferentiated pluripotent stem cells, cardiovascular progenitors, and differentiated endothelial cells, respectively. Functional characterization, including localization studies, dynamic expression analyses, epigenetic modification monitoring, and knockdown experiments in lower vertebrates, as well as murine embryos and human cells, confirmed a critical role for each lncRNA specific for each analyzed developmental stage.

CONCLUSIONS:

We have identified and functionally characterized 3 novel lncRNAs involved in vertebrate and human cardiovascular development, and we provide a comprehensive transcriptomic roadmap that sheds new light on the molecular mechanisms underlying human embryonic development, mesodermal commitment, and cardiovascular specification.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vertebrados / Sistema Cardiovascular / Regulación del Desarrollo de la Expresión Génica / Miocitos Cardíacos / Células Madre Pluripotentes / Células Endoteliales / ARN Largo no Codificante Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vertebrados / Sistema Cardiovascular / Regulación del Desarrollo de la Expresión Génica / Miocitos Cardíacos / Células Madre Pluripotentes / Células Endoteliales / ARN Largo no Codificante Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Año: 2015 Tipo del documento: Article