title: The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway.
abstract: Isl1(+) cardiovascular progenitors and their downstream progeny play a pivotal role in cardiogenesis and lineage diversification of the heart. The mechanisms that control their renewal and differentiation are largely unknown. Herein, we show that the Wnt/beta-catenin pathway is a major component by which cardiac mesenchymal cells modulate the prespecification, renewal, and differentiation of isl1(+) cardiovascular progenitors. This microenvironment can be reconstituted by a Wnt3a-secreting feeder layer with ES cell-derived, embryonic, and postnatal isl1(+) cardiovascular progenitors. In vivo activation of beta-catenin signaling in isl1(+) progenitors of the secondary heart field leads to their massive accumulation, inhibition of differentiation, and outflow tract (OFT) morphogenic defects. In addition, the mitosis rate in OFT myocytes is significantly reduced following beta-catenin deletion in isl1(+) precursors. Agents that manipulate Wnt signals can markedly expand isl1(+) progenitors from human neonatal hearts, a key advance toward the cloning of human isl1(+) heart progenitors.
authors: Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3208, 185 Cambridge Street, Boston, MA 02114-2790, USA.
authors: Yibing
authors: Y
authors: Qyang
authors: Silvia
authors: S
authors: Martin-Puig
authors: Murali
authors: M
authors: Chiravuri
authors: Shuibing
authors: S
authors: Chen
authors: Huansheng
authors: H
authors: Xu
authors: Lei
authors: L
authors: Bu
authors: Xin
authors: X
authors: Jiang
authors: Lizhu
authors: L
authors: Lin
authors: Anne
authors: A
authors: Granger
authors: Alessandra
authors: A
authors: Moretti
authors: Leslie
authors: L
authors: Caron
authors: Xu
authors: X
authors: Wu
authors: Jonathan
authors: J
authors: Clarke
authors: Makoto M
authors: MM
authors: Taketo
authors: Karl-Ludwig
authors: KL
authors: Laugwitz
authors: Randall T
authors: RT
authors: Moon
authors: Peter
authors: P
authors: Gruber
authors: Sylvia M
authors: SM
authors: Evans
authors: Sheng
authors: S
authors: Ding
authors: Kenneth R
authors: KR
authors: Chien
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000166:cytology / Q000196:embryology*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D006321:Heart / Q000196:embryology / Q000502:physiology; D006330:Heart Defects, Congenital / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C063843:insulin gene enhancer binding protein Isl-1