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Despite accumulating evidence that several pathways in various organisms are responsive to CO<jats:sub>2<\/jats:sub> elevation (hypercapnia), it has yet to be elucidated how hypercapnia activates genes and signaling pathways, or whether they interact, are integrated, or are conserved across species. Here, we performed a large-scale transcriptomic study to explore the interaction\/integration\/conservation of hypercapnia-induced genomic responses in mammals (mice and humans) as well as invertebrates (<jats:italic>Caenorhabditis elegans<\/jats:italic> and <jats:italic>Drosophila melanogaster<\/jats:italic>). We found that hypercapnia activated genes that regulate Wnt signaling in mouse lungs and skeletal muscles <jats:italic>in vivo<\/jats:italic> and in several cell lines of different tissue origin. Hypercapnia-responsive Wnt pathway homologues were similarly observed in secondary analysis of available transcriptomic datasets of hypercapnia in a human bronchial cell line, <jats:italic>flies<\/jats:italic> and <jats:italic>nematodes<\/jats:italic>. Our data suggest the evolutionarily conserved role of high CO<jats:sub>2<\/jats:sub> in regulating Wnt pathway genes.<\/jats:p>","DOI":"10.1038\/s41598-019-54683-0","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T11:04:18Z","timestamp":1575371058000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Elevated CO2 regulates the Wnt signaling pathway in mammals, Drosophila melanogaster and Caenorhabditis elegans"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7767-6584","authenticated-orcid":false,"given":"Masahiko","family":"Shigemura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Lecuona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"Angulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Dada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie B.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-3696","authenticated-orcid":false,"given":"Lynn C.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-4560","authenticated-orcid":false,"given":"S. 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