TY - JOUR
T1 - Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification
AU - Moretti, Alessandra
AU - Caron, Leslie
AU - Nakano, Atsushi
AU - Lam, Jason T.
AU - Bernshausen, Alexandra
AU - Chen, Yinhong
AU - Qyang, Yibing
AU - Bu, Lei
AU - Sasaki, Mika
AU - Martin-Puig, Silvia
AU - Sun, Yunfu
AU - Evans, Sylvia M.
AU - Laugwitz, Karl Ludwig
AU - Chien, Kenneth R.
N1 - Funding Information:
These studies were performed onsite in the Chien laboratory at MGH and the Laugwitz laboratory at the Technical University Munich. Experimental details can be provided by Alessandra Moretti ([email protected]) and Leslie Caron ([email protected]). This work was supported by unrestricted funds from MGH and the Cardiovascular Disease Program of the Harvard Stem Cell Institute (K.R.C.), a Marie Curie Excellence Team Grant from the Research Commission of the European Union (EXT - 02380) (K.L.L.); Medical Research Funds of the TU Munich (K.L.L.); the National Heart, Lung, and Blood Institute (K.R.C., Y.Q., S.E.); the French Medical Research Foundation (L.C.); and the Jean Le Ducq Foundation. We are grateful to Richard Harvey for his generosity in providing the Nkx2.5-eGFP knockin ES cell line.
PY - 2006/12/15
Y1 - 2006/12/15
N2 - Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1+ precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1+ cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1+/Nkx2.5+/flk1+ defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1+ cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types.
AB - Cardiogenesis requires the generation of endothelial, cardiac, and smooth muscle cells, thought to arise from distinct embryonic precursors. We use genetic fate-mapping studies to document that isl1+ precursors from the second heart field can generate each of these diverse cardiovascular cell types in vivo. Utilizing embryonic stem (ES) cells, we clonally amplified a cellular hierarchy of isl1+ cardiovascular progenitors, which resemble the developmental precursors in the embryonic heart. The transcriptional signature of isl1+/Nkx2.5+/flk1+ defines a multipotent cardiovascular progenitor, which can give rise to cells of all three lineages. These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1+ cardiovascular progenitor cell (MICP). The discovery of ES cell-derived MICPs suggests a strategy for cardiovascular tissue regeneration via their isolation, renewal, and directed differentiation into specific mature cardiac, pacemaker, smooth muscle, and endothelial cell types.
UR - https://www.scopus.com/pages/publications/33845457194
U2 - 10.1016/j.cell.2006.10.029
DO - 10.1016/j.cell.2006.10.029
M3 - Article
C2 - 17123592
AN - SCOPUS:33845457194
SN - 0092-8674
VL - 127
SP - 1151
EP - 1165
JO - Cell
JF - Cell
IS - 6
ER -