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We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a P \u2264 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation, including those involved in metabolism, contractility, Ca<jats:sup>2+<\/jats:sup>handling, and low-temperature catalysis. A sampling of genes showing higher expression during hibernation includes phosphofructokinase, pancreatic triacylglycerol lipase, pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum Ca<jats:sup>2+<\/jats:sup>-ATPase 2a (SERCA2a), titin, and four-and-a-half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), troponin C, phospholamban, Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent protein kinase II (CaMKII), calmodulin, and four subunits of cytochrome c oxidase.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00076.2005","type":"journal-article","created":{"date-parts":[[2005,8,3]],"date-time":"2005-08-03T02:53:41Z","timestamp":1123037621000},"page":"227-234","source":"Crossref","is-referenced-by-count":83,"title":["Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal"],"prefix":"10.1152","volume":"23","author":[{"given":"Katharine M.","family":"Brauch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirish D.","family":"Dhruv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Hanse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8392"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1101\/gr.7.10.986"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.4.R1186"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/0011-2240(91)90042-M"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/ng0893-332"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.2741\/Brushia"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00076.2001"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/0011-2240(72)90037-5"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00008.2003"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(97)00389-2"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0171-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1006\/cryo.2000.2254"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000117769.88862.F8"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1042\/bst0311143"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(85)90090-4"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00181"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1997.272.4.R1121"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Lyman CP, Willis JS, Malan A, and Wang LCH.Hibernation and Torpor in Mammals and Birds. 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