Identification of new cardiac progenitors

Mammalian Development Laboratory / Saga Group

Sfrp5 identifies murine cardiac progenitors for all myocardial structures except for the right ventricle

Fujii Masayuki, Akane Sakaguchi, Ryo Kamata, Masataka Nagao, Shilvia M. Evans, Masao Yoshizumi, Akihiko Shimono, Yumiko Saga, and Hiroki Kokubo

Nature Communications. DOI:10.1038/NCOMMS1466

Upon acquirement of pulmonary circulation, the ancestral heart may have been remodelled coincidently with, or accompanied by, the production and rearrangement of progenitor cells. However, the progenitor populations that give rise to the left ventricle (LV) and sinus venosus (SV) are still ambiguous. Here we show that the expression of Secreted frizzled-related protein Sfrp5 in the mouse identifies common progenitors for the outflow tract (OFT), LV, atrium and SV but not the right ventricle (RV). Sfrp5 expression begins at the lateral sides of the cardiac crescent, excluding early differentiating regions, and continues in the venous pole, which gives rise to the SV. Lineage-tracing analysis revealed that descendants of Sfrp5-expressing cells at E7.5 contribute not only to the SV but also to the LV, atria and OFT and are found also in the dorsal splanchnic mesoderm accompanied by the expression of the secondary heart field marker, Islet1. These findings provide insight into the arrangement of cardiac progenitors for systemic circulation. This study was conducted as a collaboration research with Dr. Kokubo who used to be an assistant professor in Mammalian Development Lab and currently a lecturer of Hiroshima University.

Figure1

Upper panels show the expression area ofSfrp5 (orange) andIslet1 (light green) at E7.5 (left) and the distribution of descendant cells at E9.5 (right).
The lower panel shows the lineage contribution of the heart. Mesp1-positive mesodermal cells are common cardiac precursors.TransientIslet1-expressing cells that do not expressSfrp5 contribute to the RV, OFT and atrium (green). Sfrp5-positive cells contribute to the LV, atrium and OFT (orange) the SV