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Despite extensive studies, our understanding remains incomplete. Notably,\n                    <jats:italic>Shh<\/jats:italic>\n                    signaling is suggested to promote cardiac differentiation, while paradoxically preventing premature differentiation of SHF progenitors. In this study, we elucidate the role of\n                    <jats:italic>Shh<\/jats:italic>\n                    signaling in the earliest phase of cardiac differentiation. Our meta\u2010analysis of single\u2010cell RNA sequencing suggests that cardiogenic nascent mesoderm cells expressing the bHLH transcription factor\n                    <jats:italic>Mesp1<\/jats:italic>\n                    interact with axial mesoderm via Hh signaling. Activation of Hh signaling using a Smoothened agonist delayed or suppressed the differentiation of primitive streak cells expressing T\u2010box transcription factor\n                    <jats:italic>T<\/jats:italic>\n                    to\n                    <jats:italic>Mesp1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    nascent mesoderm cells both in vitro and ex vivo. Conversely, inhibition of Hh signaling by cyclopamine facilitated cardiac differentiation. The reduction of\n                    <jats:italic>Eomes<\/jats:italic>\n                    , an inducer of\n                    <jats:italic>Mesp1<\/jats:italic>\n                    , by Hh signaling appears to be the underlying mechanism of this phenomenon. Our data suggest that SHH secreted from axial mesoderm inhibits premature differentiation of\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    cells to\n                    <jats:italic>Mesp1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    nascent mesoderm cells, thereby regulating the pace of cardiac differentiation. These findings enhance our comprehension of\n                    <jats:italic>Shh<\/jats:italic>\n                    signaling in cardiac development, underscoring its crucial role in early cardiac differentiation.\n                  <\/jats:p>","DOI":"10.1111\/dgd.12955","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T05:33:47Z","timestamp":1736400827000},"page":"75-84","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sonic Hedgehog signaling regulates the optimal differentiation pace from early\u2010stage mesoderm to cardiogenic mesoderm in mice"],"prefix":"10.1111","volume":"67","author":[{"given":"Satoshi","family":"Inoue","sequence":"first","affiliation":[{"name":"Division of Anatomy and Developmental Biology, Department of Anatomy, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"},{"name":"Department of Pediatrics, Graduate School 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Pediatrics, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Developmental Biology, Department of Anatomy, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Saba","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Developmental Biology, Department of Anatomy, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"},{"name":"Department of Radiology, Graduate School of Medical Science Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Developmental Biology, Department of 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