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A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development.

Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Although it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells, the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development, including the homeobox gene MEIS2. Using the zebrafish model, we demonstrate that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions.

Pubmed ID: 22981225

Authors

  • Paige SL
  • Thomas S
  • Stoick-Cooper CL
  • Wang H
  • Maves L
  • Sandstrom R
  • Pabon L
  • Reinecke H
  • Pratt G
  • Keller G
  • Moon RT
  • Stamatoyannopoulos J
  • Murry CE

Journal

Cell

Publication Data

September 28, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: F30 HL095343
  • Agency: NHLBI NIH HHS, Id: F30 HL095343
  • Agency: NIGMS NIH HHS, Id: P01 GM081619
  • Agency: NIGMS NIH HHS, Id: P01 GM081719
  • Agency: NHLBI NIH HHS, Id: P01 HL094374
  • Agency: NHLBI NIH HHS, Id: P01 HL094374
  • Agency: NHLBI NIH HHS, Id: R01 HL064387
  • Agency: NHLBI NIH HHS, Id: R01 HL084642
  • Agency: NHLBI NIH HHS, Id: R01 HL084642
  • Agency: NHLBI NIH HHS, Id: R01 HL64387
  • Agency: NIAMS NIH HHS, Id: R03 AR057477
  • Agency: NIAMS NIH HHS, Id: R03 AR057477
  • Agency: NHGRI NIH HHS, Id: R90HG004152
  • Agency: NHLBI NIH HHS, Id: U01 HL100405
  • Agency: NHLBI NIH HHS, Id: U01 HL100405
  • Agency: NHGRI NIH HHS, Id: U54 HG004592
  • Agency: NHGRI NIH HHS, Id: U54HG004592

Mesh Terms

  • Animals
  • Cell Differentiation
  • Chromatin
  • Embryonic Stem Cells
  • Epigenesis, Genetic
  • Heart
  • Homeodomain Proteins
  • Humans
  • Myocardium
  • Zebrafish
  • Zebrafish Proteins