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

Masayuki Fujii; Akane Sakaguchi; Ryo Kamata; Masataka Nagao; Yutaka Kikuchi; Silvia M Evans; Masao Yoshizumi; Akihiko Shimono; Yumiko Saga; Hiroki Kokubo

doi:10.1038/ncomms14664

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

Nat Commun. 2017 Mar 13:8:14664. doi: 10.1038/ncomms14664.

Authors

Masayuki Fujii¹, Akane Sakaguchi^{2

3}, Ryo Kamata¹, Masataka Nagao⁴, Yutaka Kikuchi⁵, Silvia M Evans⁶, Masao Yoshizumi¹, Akihiko Shimono⁷, Yumiko Saga^{2

3}, Hiroki Kokubo¹

Affiliations

¹ Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan.
² Department of Mammalian Development, National Institute of Genetics, Mishima 411-8540 Japan.
³ The Graduate University for Advanced Studies (SOKENDAI), Hayama, Kanagawa 240-0193, Japan.
⁴ Department of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima 734-8551, Japan.
⁵ Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-2 Kagamiyama, Higashi-hiroshima 739-8511, Japan.
⁶ Department of Medicine, School of Medicine UC San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
⁷ Center for Developmental Biology (CDB), RIKEN Kobe, 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe 650-0047, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Biomarkers / metabolism
Body Patterning / genetics
Cell Lineage / genetics
Cell Tracking / methods
Coronary Sinus / cytology
Coronary Sinus / growth & development
Coronary Sinus / metabolism*
Embryo, Mammalian
Fibroblast Growth Factor 10 / genetics
Fibroblast Growth Factor 10 / metabolism
Gene Expression
Heart Atria / cytology
Heart Atria / growth & development
Heart Atria / metabolism*
Heart Ventricles / cytology
Heart Ventricles / growth & development
Heart Ventricles / metabolism*
Intercellular Signaling Peptides and Proteins / genetics*
Intercellular Signaling Peptides and Proteins / metabolism
LIM-Homeodomain Proteins / genetics
LIM-Homeodomain Proteins / metabolism
MEF2 Transcription Factors / genetics
MEF2 Transcription Factors / metabolism
Mesoderm / cytology
Mesoderm / growth & development
Mesoderm / metabolism
Mice
Mice, Transgenic
Myocardium / cytology
Myocardium / metabolism*
Stem Cells / cytology
Stem Cells / metabolism*
T-Box Domain Proteins / genetics
T-Box Domain Proteins / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Adaptor Proteins, Signal Transducing
Biomarkers
Fgf10 protein, mouse
Fibroblast Growth Factor 10
Intercellular Signaling Peptides and Proteins
LIM-Homeodomain Proteins
MEF2 Transcription Factors
Mef2c protein, mouse
Sfrp5 protein, mouse
T-Box Domain Proteins
Tbx1 protein, mouse
Transcription Factors
insulin gene enhancer binding protein Isl-1