Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors.
Identification of multipotent cardiac progenitors has provided important insights into the mechanisms of myocardial lineage specification, yet has done little to clarify the origin of the endocardium. Despite its essential role in heart development, characterization of the endocardial lineage has been limited by the lack of specific markers of this early vascular subpopulation. To distinguish endocardium from other vasculature, we generated an NFATc1-nuc-LacZ BAC transgenic mouse line capable of labeling this specific endothelial subpopulation at the earliest stages of cardiac development. To further characterize endocardiogenesis, embryonic stem cells (ESCs) derived from NFATc1-nuc-LacZ blastocysts were utilized to demonstrate that endocardial differentiation in vitro recapitulates the close temporal-spatial relationship observed between myocardium and endocardium seen in vivo. Endocardium is specified as a cardiac cell lineage, independent from other vascular populations, responding to BMP and Wnt signals that enhance cardiomyocyte differentiation. Furthermore, a population of Flk1+ cardiovascular progenitors, distinct from hemangioblast precursors, represents a mesodermal precursor of the endocardial endothelium, as well as other cardiovascular lineages. Taken together, these studies emphasize that the endocardium is a unique cardiac lineage and provides further evidence that endocardium and myocardium are derived from a common precursor.
Misfeldt
Andrew M
AM
Department of Pediatrics, Division of Cardiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Boyle
Scott C
SC
Tompkins
Kevin L
KL
Bautch
Victoria L
VL
Labosky
Patricia A
PA
Baldwin
H Scott
HS
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000502:physiology*; D004699:Endocardium / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D050778:NFATC Transcription Factors / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D000943:Antigens, Differentiation; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2