Your browser doesn't support javascript.
loading
Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency.
Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A; Doench, John; Rinn, John L; Daley, George Q; Meissner, Alexander; Lander, Eric S; Mikkelsen, Tarjei S.
Afiliação
  • Cacchiarelli D; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Trapnell C; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Ziller MJ; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Soumillon M; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Cesana M; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Boston Children's Hospital and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, B
  • Karnik R; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Donaghey J; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Smith ZD; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Ratanasirintrawoot S; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Boston Children's Hospital and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, B
  • Zhang X; Broad Institute, Cambridge, MA 02142, USA.
  • Ho Sui SJ; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • Wu Z; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Boston Children's Hospital and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, B
  • Akopian V; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Gifford CA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Doench J; Broad Institute, Cambridge, MA 02142, USA.
  • Rinn JL; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Daley GQ; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Boston Children's Hospital and Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, B
  • Meissner A; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
  • Lander ES; Broad Institute, Cambridge, MA 02142, USA.
  • Mikkelsen TS; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA. Electronic address: tarjei@broadinstitute.org.
Cell ; 162(2): 412-424, 2015 Jul 16.
Article em En | MEDLINE | ID: mdl-26186193
ABSTRACT
Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here, we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PAPERCLIP.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reprogramação Celular / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Reprogramação Celular / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos