Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart

Yuichi Tomita, Keisuke Matsumura, Yoshio Wakamatsu, Yumi Matsuzaki, Isao Shibuya, Haruko Kawaguchi, Masaki Ieda, Sachiko Kanakubo, Takuya Shimazaki, Satoshi Ogawa, Noriko Osumi, Hideyuki Okano, Keiichi Fukuda

Research output: Contribution to journalArticlepeer-review

277 Citations (Scopus)


Arodent cardiac side population cell fraction formed clonal spheroids in serum-free medium, which expressed nestin, Musashi-1, and multidrug resistance transporter gene 1, markers of undifferentiated neural precursor cells. These markers were lost following differentiation, and were replaced by the expression of neuron-, glial-, smooth muscle cell-, or cardiomyocyte-specific proteins. Cardiosphere-derived cells transplanted into chick embryos migrated to the truncus arteriosus and cardiac outflow tract and contributed to dorsal root ganglia, spinal nerves, and aortic smooth muscle cells. Lineage studies using double transgenic mice encoding protein 0-Cre/Floxed-EGFP revealed undifferentiated and differentiated neural crest-derived cells in the fetal myocardium. Undifferentiated cells expressed GATA-binding protein 4 and nestin, but not actinin, whereas the differentiated cells were identified as cardiomyocytes. These results suggest that cardiac neural crest-derived cells migrate into the heart, remain there as dormant multipotent stem cells-and under the right conditions-differentiate into cardiomyocytes and typical neural crest-derived cells, including neurons, glia, and smooth muscle.

Original languageEnglish
Pages (from-to)1135-1146
Number of pages12
JournalJournal of Cell Biology
Issue number7
Publication statusPublished - 2005 Sept 26

ASJC Scopus subject areas

  • Cell Biology


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