利用生物信息学方法解析自噬相关基因在人体红细胞终末分化各阶段的动态表达
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摘要
为了探究自噬相关基因在人体红细胞终末分化各阶段的表达概况,利用生物信息学方法对人体终末分化各阶段红细胞转录组测序(RNA sequencing,RNA-Seq)数据中自噬相关基因的表达进行提取并分析。结果表明,自噬相关基因在红细胞终末分化各阶段呈现不同的表达模式;在红细胞终末分化的早期,超过50%的自噬相关基因呈现高表达状态;原始红细胞及早幼红细胞中高表达的自噬相关基因富集的生物学过程主要包括细胞自噬及其调节、蛋白质的磷酸化及囊泡的运输,而线粒体自噬相关基因主要在中幼红细胞及晚幼红细胞阶段高表达。研究发现,自噬相关基因在人体红细胞终末分化各阶段的表达呈现动态变化;不同阶段的红细胞中高表达的自噬相关基因及其富集的生物学过程均不同。
In order to analyze the dynamic expression of autophagy related genes in human terminal erythroid differentiation, based on their RNA-Seq data, the expression of autophagy related genes in human terminal erythroid differentiation were extracted and analyzed by using bioinformatics methods. Results revealed that the expression patterns of autophagy related genes in different stages of terminal erythroid differentiation were different. In the early stage of terminal erythroid differentiation, more than 50% of the autophagy related genes were highly expressed, and the biological processes which autophagy related genes with high expression level in proerythroblast and basophilic erythroblast enriched included autophagy and its regulation, proteins phosphorylation and transport of vesicles. Besides, mitophagy related genes were highly expressed in polychromatic erythroblast and orthochromatic erythroblast. The research indicated that the expression of autophagy related genes in human terminal erythroid differentiation showed dynamic changes. In addition, autophagy related genes with high expression level in different stages were different, as well as the biological processes they enriched.
In order to analyze the dynamic expression of autophagy related genes in human terminal erythroid differentiation, based on their RNA-Seq data, the expression of autophagy related genes in human terminal erythroid differentiation were extracted and analyzed by using bioinformatics methods. Results revealed that the expression patterns of autophagy related genes in different stages of terminal erythroid differentiation were different. In the early stage of terminal erythroid differentiation, more than 50% of the autophagy related genes were highly expressed, and the biological processes which autophagy related genes with high expression level in proerythroblast and basophilic erythroblast enriched included autophagy and its regulation, proteins phosphorylation and transport of vesicles. Besides, mitophagy related genes were highly expressed in polychromatic erythroblast and orthochromatic erythroblast. The research indicated that the expression of autophagy related genes in human terminal erythroid differentiation showed dynamic changes. In addition, autophagy related genes with high expression level in different stages were different, as well as the biological processes they enriched.
引文
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[2] Klionsky D J,Emr S D.Autophagy as a regulated pathway of cellular degradation[J].Science,2000,290(5497):1717-1721.
[3] Gregory C J,Eaves A C.Human marrow cells capable of erythropoietic differentiation in vitro:Definition of three erythroid colony responses[J].Blood,1977,49(6):855-864.
[4] Grosso R,Fader C M,Colombo M I.Autophagy:A necessary event during erythropoiesis[J].Blood Rev.,2017,31(5):300-305.
[5] An X,Schulz V P,Li J,et al..Global transcriptome analyses of human and murine terminal erythroid differentiation[J].Blood,2014,123(22):3466-3477.
[6] Homma K,Suzuki K,Sugawara H.The autophagy database:An all-inclusive information resource on autophagy that provides nourishment for research[J].Nucl.Acids Res.,2011,39:986-990.
[7] Türei D,F?ldvári-Nagy L,Fazekas D,et al..Autophagy Regulatory Network——A systems-level bioinformatics resource for studying the mechanism and regulation of autophagy[J].Autophagy,2015,11(1):155-165.
[8] Huang D W,Sherman B T,Lempicki R A.Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources[J].Nat.Protoc.,2009,4(1):44-57.
[9] Supek F,Bosnjak M,Skunca N,et al..REVIGO summarizes and visualizes long lists of gene ontology terms[J].PLoS ONE,2011,6(7):e21800.
[10] Fader C M,Colombo M I.Multivesicular bodies and autophagy in erythrocyte maturation[J].Autophagy,2006,2(2):122-125.
[11] Zhang J,Wu K,Xiao X,et al..Autophagy as a regulatory component of erythropoiesis[J].Int.J.Mol.Sci.,2015,16(2):4083-4094.
[12] Cao Y,Cai J,Li X,et al..Autophagy governs erythroid differentiation both in vitro and in vivo[J].Hematology,2016,21(4):225-233.
[13] Kundu M,Lindsten T,Yang C Y,et al..Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation[J].Blood,2008,112(4):1493-1502.
[14] Lemasters J J.Selective mitochondrial autophagy,or mitophagy,as a targeted defense against oxidative stress,mitochondrial dysfunction,and aging[J].Rejuv.Res.,2005,8(1):3-5.
[15] Mortensen M,Ferguson D J,Edelmann M,et al..Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo[J].Proc.Natl.Acad.Sci.USA,2010,107(2):832-837.
[16] Mortensen M,Ferguson D J,Simon A K.Mitochondrial clearance by autophagy in developing erythrocytes:Clearly important,but just how much so?[J].Cell Cycle,2010,9(10):1901-1906.
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