title: A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development.
abstract: 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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, 98109, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Paige
authors.forename: Sean
authors.initials: S
authors.lastname: Thomas
authors.forename: Cristi L
authors.initials: CL
authors.lastname: Stoick-Cooper
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Lisa
authors.initials: L
authors.lastname: Maves
authors.forename: Richard
authors.initials: R
authors.lastname: Sandstrom
authors.forename: Lil
authors.initials: L
authors.lastname: Pabon
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pratt
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
authors.forename: John
authors.initials: J
authors.lastname: Stamatoyannopoulos
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin; D053595:Embryonic Stem Cells / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000166:cytology*; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D029961:Zebrafish Proteins; C491173:meis2b protein, zebrafish