The Transcriptome Responses of Cardiomyocyte Exposed to Hypothermia. Homo sapiens

Hypothermia affects the body in positive and negative consequences. In cardiac, hypothermia depresses myocardial contraction, slows conduction, and decreases metabolic rate. However, little is known about the molecular mechanism. Here we compare the genes expression of human adult ventricular cardiomyocyte cells (AC16) treated with hypothermia, trying to find changes under different temperatures and then elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology enrichment analysis revealed that genes related to gene transcriptions, protein and lipid metabolic were significantly enriched. KEGG analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in response to hypothermia. A set of TFs (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. These identified DEGs, pathways and predicted TF could facilitate further investigations of the detailed molecular mechanisms, making it possible to take advantage of the potential applications of hypothermia in broader ranger Overall design: AC16 cell lines was treated by hypothermia (n=3) and control group (n=3) for 6 hours.

低温对机体可产生正反两方面的影响。在心脏系统中，低温会抑制心肌收缩、减慢传导速度并降低代谢率。然而，目前对其分子机制的研究仍较为匮乏。
本研究对经低温处理的人类成年心室心肌细胞（AC16）的基因表达谱开展对比分析，旨在探明不同温度条件下的基因表达变化，并筛选出可能在低温应答过程中发挥关键作用的候选基因。本研究通过微阵列杂交技术共鉴定出2413个差异表达基因（differentially expressed genes, DEGs），为后续研究提供了充足的数据基础。
基因本体（Gene Ontology, GO）富集分析结果显示，与基因转录、蛋白质及脂质代谢相关的基因呈现显著富集。京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析显示，DEGs显著富集于转化生长因子-β（transforming growth factor-β, TGF-β）通路以及细胞因子-细胞因子受体相互作用通路，上述通路可能在低温应答中发挥重要调控作用。
本研究同时鉴定出一组转录因子（transcription factors, TFs），包括CPBP、Churchill、NF-AT1、GKLF、SRY、ZNF333、ING4、肌细胞生成素（myogenin）、DRI1及CRX，它们作为关键节点的功能层，可将低温信号传导至转录组。
本研究鉴定得到的DEGs、相关通路以及预测的转录因子，可为深入解析低温应答的具体分子机制提供重要支撑，同时也为拓展低温疗法的潜在应用范围提供了可行方向。
实验整体设计：将AC16细胞系分为低温处理组（n=3）与对照组（n=3），两组细胞均接受6小时的低温处理。