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DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells.
Daneshvar, Kaveh; Pondick, Joshua V; Kim, Byeong-Moo; Zhou, Chan; York, Samuel R; Macklin, Jillian A; Abualteen, Ameed; Tan, Bo; Sigova, Alla A; Marcho, Chelsea; Tremblay, Kimberly D; Mager, Jesse; Choi, Michael Y; Mullen, Alan C.
Afiliação
  • Daneshvar K; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Pondick JV; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Kim BM; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Zhou C; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • York SR; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Macklin JA; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Abualteen A; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Tan B; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; School of Fundamental Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
  • Sigova AA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Marcho C; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
  • Tremblay KD; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
  • Mager J; Department of Veterinary and Animal Sciences, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
  • Choi MY; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Mullen AC; Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: acmullen@mgh.harvard.edu.
Cell Rep ; 17(2): 353-365, 2016 10 04.
Article em En | MEDLINE | ID: mdl-27705785
ABSTRACT
Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript reveal that DIGIT is required for definitive endoderm differentiation. In addition, we identify the mouse ortholog of DIGIT and show that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator of definitive endoderm.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Proteína Smad3 / Proteína Goosecoid / RNA Longo não Codificante Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diferenciação Celular / Proteína Smad3 / Proteína Goosecoid / RNA Longo não Codificante Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos