{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:07:20Z","timestamp":1789697240176,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Coccidioides immitis and C.\u00a0posadasii are dimorphic fungi that transform from mycelia with internal arthroconidia in the soil to a tissue form known as a spherule in mammals. This process can be recapitulated in vitro by increasing the temperature, CO2 and changing other culture conditions. In this study, we have analyzed changes in gene expression in mycelia and young and mature spherules. Genes that were highly upregulated in young spherules include a spherule surface protein and iron and copper membrane transporters. Genes that are unique to Coccidioides spp. are also overrepresented in this group, suggesting that they may be important for spherule differentiation. Enriched GO terms in young spherule upregulated genes include oxidation-reduction, response to stress and membrane proteins. Downregulated genes are enriched for transcription factors, especially helix\u2013loop\u2013helix and C2H2 type zinc finger domain-containing proteins, which is consistent with the dramatic change in transcriptional profile. Almost all genes that are upregulated in young spherules remain upregulated in mature spherules, but a small number of genes are differentially expressed in those two stages of spherule development. Mature spherules express more Hsp31 and amylase and less tyrosinase than young spherules. Some expression of transposons was detected and most of the differentially expressed transposons were upregulated in spherules.<\/jats:p>","DOI":"10.3390\/jof7050366","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:06:12Z","timestamp":1620381972000},"page":"366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Transcriptional Analysis of Coccidioides immitis Mycelia and Spherules by RNA Sequencing"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1669-8066","authenticated-orcid":false,"given":"Aaron F.","family":"Carlin","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-7538","authenticated-orcid":false,"given":"Sinem","family":"Beyhan","sequence":"additional","affiliation":[{"name":"J. Craig Venter Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-6795","authenticated-orcid":false,"given":"Jes\u00fas F.","family":"Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Plant Pathology, Institute for Integrative Genome Biology, University of California-Riverside, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-0020","authenticated-orcid":false,"given":"Jason E.","family":"Stajich","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Plant Pathology, Institute for Integrative Genome Biology, University of California-Riverside, Riverside, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suganya","family":"Viriyakosol","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Fierer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"},{"name":"Infectious Diseases Section, VA Healthcare San Diego, San Diego, CA 92161, USA"},{"name":"Department of Pathology, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-7302","authenticated-orcid":false,"given":"Theo N.","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"},{"name":"Department of Pathology, U.C. San Diego School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00550-16","DOI":"10.1128\/mBio.00550-16","article-title":"Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever","volume":"7","author":"Engelthaler","year":"2016","journal-title":"MBio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1080\/21505594.2018.1509667","article-title":"Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity","volume":"9","author":"Kirkland","year":"2018","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1128\/CMR.00005-13","article-title":"Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis","volume":"26","author":"Nguyen","year":"2013","journal-title":"Clin. 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