Abstract
The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development. However, the mechanisms that direct atrial versus ventricular specification remain largely unknown. Here we report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells (<5%) of the differentiated heart. These progenitors are specified during gastrulation, when they transiently express Foxa2, a gene not previously implicated in cardiac development. Importantly, Foxa2+ cells contribute to previously identified progenitor populations in a defined pattern and ratio. Lastly, we describe an analogous Foxa2+ population during differentiation of embryonic stem cells. Together, these findings provide insight into the developmental origin of ventricular and atrial cells, and may lead to the establishment of new strategies for generating chamber-specific cell types from pluripotent stem cells.
Highlights
The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development
Several selective fate-mapping studies have identified cardiac progenitors at the gastrulation stage, further implying early specification of the cardiac lineages[12,13,14,15]. These studies suggest that the cardiac mesoderm (CM) is formed from the posterior epiblast and migrates anteriorly, where it takes up residence beneath the head folds to form the cardiac crescent (CC)
The key regulators of these cell-fate specification events have been challenging to study, largely due to the inability to prospectively identify early chamber-specific progenitor populations. To identify such cardiac progenitor populations during early embryogenesis, we turned our attention to genes that are known to be critical for cell-fate specification events during gastrulation and that are expressed in the prospective mesoderm in the primitive streak (PS)
Summary
The recent identification of progenitor populations that contribute to the developing heart in a distinct spatial and temporal manner has fundamentally improved our understanding of cardiac development. We report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells (o5%) of the differentiated heart These progenitors are specified during gastrulation, when they transiently express Foxa[2], a gene not previously implicated in cardiac development. More recent lineage tracing experiments using Mesp[1] or regulatory regions for Smarcd[3] identified cells during gastrulation that have already acquired a cardiac fate[20,21] These efforts have greatly advanced our knowledge of the timing of heart specification, many open questions remain with respect to the mechanistic regulation of these early migration and specification events. Our data provide an approach to genetically label a ventricular cardiac progenitor population as early as during gastrulation, enabling the isolation and characterization of prospective ventricular cells at any stage during development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
