Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several stud...Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that multiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.展开更多
利用Illumina HD SNP技术对484头中国西门塔尔牛SCD1基因的遗传变异及其与部分肉质性状的相关性进行了分析。结果表明,该群体中存在7个SCD1基因的SNP位点。SCD1基因第4内含子存在A8605G、A9229G与A10050C 3个SNP位点;第5内含子存在1个SN...利用Illumina HD SNP技术对484头中国西门塔尔牛SCD1基因的遗传变异及其与部分肉质性状的相关性进行了分析。结果表明,该群体中存在7个SCD1基因的SNP位点。SCD1基因第4内含子存在A8605G、A9229G与A10050C 3个SNP位点;第5内含子存在1个SNP位点A12304G;3’UTR区存在A13655G、C14790T与A15565G 3个位点。A8605G位点的B等位基因为优势等位基因,频率为0.748,其他位点等位基因频率在0.4～0.6之间。χ2检验结果显示,SCD1基因的所有SNPs均处于哈代-温伯格平衡状态(P>0.05)。SCD1基因的7个SNPs位点全部为中度多态,杂合度和有效等位基因数均较高。SCD1基因SNP多态性与肉质性状的关联分析表明,SCD1基因对肌内脂肪含量、剪切力、大理石花纹等级和脂肪颜色有一定的影响,可以作为改善牛肉质量进行标记辅助选择的重要候选基因。展开更多
本研究利用生物信息学方法分析和预测牛SCD1基因的理化特性和编码产物的结构。结果表明牛SCD1基因编码359个氨基酸,平均分子质量为41.71 k Da;组成蛋白为不稳定的水溶性蛋白,三级结构由α-螺旋和无规则卷曲组成,并且牛SCD1基因氨基酸序...本研究利用生物信息学方法分析和预测牛SCD1基因的理化特性和编码产物的结构。结果表明牛SCD1基因编码359个氨基酸,平均分子质量为41.71 k Da;组成蛋白为不稳定的水溶性蛋白,三级结构由α-螺旋和无规则卷曲组成,并且牛SCD1基因氨基酸序列和山羊亲缘关系最近。牛SCD1基因的生物信息学分析为进一步研究牛SCD1基因的遗传特性和生理机制奠定了基础。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82192910,82192911)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-D-202207).
文摘Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that multiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.
文摘利用Illumina HD SNP技术对484头中国西门塔尔牛SCD1基因的遗传变异及其与部分肉质性状的相关性进行了分析。结果表明,该群体中存在7个SCD1基因的SNP位点。SCD1基因第4内含子存在A8605G、A9229G与A10050C 3个SNP位点;第5内含子存在1个SNP位点A12304G;3’UTR区存在A13655G、C14790T与A15565G 3个位点。A8605G位点的B等位基因为优势等位基因,频率为0.748,其他位点等位基因频率在0.4～0.6之间。χ2检验结果显示,SCD1基因的所有SNPs均处于哈代-温伯格平衡状态(P>0.05)。SCD1基因的7个SNPs位点全部为中度多态,杂合度和有效等位基因数均较高。SCD1基因SNP多态性与肉质性状的关联分析表明,SCD1基因对肌内脂肪含量、剪切力、大理石花纹等级和脂肪颜色有一定的影响,可以作为改善牛肉质量进行标记辅助选择的重要候选基因。
文摘本研究利用生物信息学方法分析和预测牛SCD1基因的理化特性和编码产物的结构。结果表明牛SCD1基因编码359个氨基酸,平均分子质量为41.71 k Da;组成蛋白为不稳定的水溶性蛋白,三级结构由α-螺旋和无规则卷曲组成,并且牛SCD1基因氨基酸序列和山羊亲缘关系最近。牛SCD1基因的生物信息学分析为进一步研究牛SCD1基因的遗传特性和生理机制奠定了基础。
