早期停育胚胎的滋养层细胞相关基因与特征分析

doi:10.16288/j.yczz.20-144

遗传 ›› 2020, Vol. 42 ›› Issue (10): 1004-1016.doi: 10.16288/j.yczz.20-144

早期停育胚胎的滋养层细胞相关基因与特征分析

张悦¹, 冯颖², 马芳^1,³()

^1. 四川大学华西第二医院教育部“妇儿疾病与出生缺陷”重点实验室,成都 610041;
^2. 四川大学华西基础医学与法医学院,成都 610041
^3. 四川大学华西第二医院妇产科,成都 610041

收稿日期:2020-08-08 修回日期:2020-10-02 出版日期:2020-10-20 发布日期:2020-10-15
通讯作者: 马芳 E-mail:mafangmed@126.com
作者简介:张悦,在读硕士研究生,专业方向：母婴医学。E-mail: zhangyue@stu.scu.edu.cn
基金资助:
国家自然科学基金项目编号(31771662);国家科技重大专项资助编号(2018YFC1002803-3)

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

Yue Zhang¹, Ying Feng², Fang Ma^1,³()

^1. Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
^2. West China School of Basic Medical Sciences & Forensic Medicine, Chengdu 610041, China;
^3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China

Received:2020-08-08 Revised:2020-10-02 Online:2020-10-20 Published:2020-10-15
Contact: Ma Fang E-mail:mafangmed@126.com
Supported by:
Supported by the National Nature Science Foundation of China No(31771662);the National Science and Technology Major Project No(2018YFC1002803-3)

摘要/Abstract

摘要：

滋养层细胞对维持正常胚胎植入、生长发育有重要作用。研究停育胚胎的滋养层细胞的基因表达差异有助于了解胚胎发育停止或不良妊娠结局的发生发展机制。本研究通过对26例正常妊娠、胚胎停育妇女的绒毛组织进行全转录组测序和初步生物信息学分析,发现胚胎停育组存在436个差异基因,其中406个mRNA为显著上调基因,32个mRNA为显著下调基因。基因富集分析显示这些基因显著富集于免疫相关功能、细胞间黏附等方面,如淋巴细胞激活、髓系细胞激活、细胞外基质及胶原连接等,其潜在调控通路富集到补体及凝血级联反应和细胞外基质降解等条目。此外,本研究利用WGCNA共表达分析得到和差异基因存在共表达关系的lncRNA。根据模块功能不同,绘制了两个网络图,可得4个关键基因,分别为VSIG4、C1QC、CD36和SPP1。本研究得到的这些差异基因可作为对胚胎停育具有潜在影响的关键分子,所富集到的条目可为深入了解胚胎发育停止或不良妊娠结局的病因及机制提供理论依据及方向。

关键词: 滋养层细胞, RNA测序, 富集分析, 基因特征

Abstract:

Trophoblast cells play essential roles in the maintenance of normal embryo implantation, growth and development. The study of abnormal gene changes in trophoblastic cells from arrested embryos is helpful to understand the developmental mechanism of embryo developmental cessation or adverse pregnancy outcomes. In this study, we sequenced and analyzed the transcriptomes of the villi from ten women who have undergone abortion with either normal pregnancy or embryo development cessation. We found that there were 436 differentially expressed genes, of which 406 mRNA were significantly up-regulated and 32 mRNA were significantly down-regulated. Gene enrichment analysis showed that these genes were significantly enriched in immune-related functions and intercellular adhesion, such as lymphocyte activation, myeloid cell activation, extracellular matrix and collagen junction. And their potential regulatory pathways were enriched in terms of complement and coagulation cascade, extracellular matrix degradation. In addition, in this study the co-expression analysis of WGCNA was used to obtain the lncRNA with co-expression relationship with the differential genes. According to the different functions of the modules, two network diagrams were drawn, and four key genes were obtained, namely VSIG4, C1QC, CD36 and SPP1. These differential genes obtained in this study can be used as key molecules with potential effects on embryo development cessation. The enriched entries can provide a theoretical basis and new direction for further understanding of the etiology and mechanism of embryo development cessation or adverse pregnancy outcomes.

Key words: trophoblast, RNA-seq, enrichment analysis, genetic traits

张悦, 冯颖, 马芳. 早期停育胚胎的滋养层细胞相关基因与特征分析[J]. 遗传, 2020, 42(10): 1004-1016.

Yue Zhang, Ying Feng, Fang Ma. Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation[J]. Hereditas(Beijing), 2020, 42(10): 1004-1016.

图/表 8

表1

表2

图1

图2

图3

表3

差异mRNA的KEGG富集分析(置信度最高的前10条信号通路)"

通路二级分类(B类)	通路	P值	q值	通路号	富集到的基因
免疫系统 (immune system)	补体及凝血级联反应(complement and coagulation cascades)	3.70E-07	9.07E-05	ko04610	C7、CLU、F13A1、VSIG4、C1QC、ITGB2、ITGAM、C3AR1、C1QB、C1QA、C5AR1、CFD、CR1
信号分子与相互作用 (signaling molecules and interaction)	细胞外基质 (cell adhesion molecules)	3.78E-07	1.16E-03	ko04514	ITGAL、SPP1、CD4、PTPRC、SIGLEC1、NRCAM、MAG、CD36、LRRC4、VTCN1、ITGB2、NFASC、ITGAM、HLA-DOA、HLA-DRA、HLA-C、HLA-G、HLA-A、HLA-B
运输和分解代谢 (transport and catabolism)	吞噬体 (phagosome)	2.54E-06	2.07E-04	ko04145	MSR1、CORO1A、COMP、NCF2、CD36、TLR2、FCGR2A、FCGR1A、PLA2R1、ITGB2、CTSS、CYBB、ITGAM、CD14、HLA-DOA、HLA-DRA、HLA-C、HLA-G、HLA-A、HLA-B、MRC1、RAB7B
感染性疾病 (infectious diseases)	金黄色葡萄球菌感染 (Staphylococcus aureus infection)	3.84E-06	2.35E-04	ko05150	ITGAL、FCGR2A、FCGR1A、C1QC、ITGB2、ITGAM、FPR2、FPR1、C3AR1、C1QB、C1QA、C5AR1、CFD、HLA-DOA、HLA-DRA
感染性疾病 (infectious diseases)	阿米巴病 (amoebiasis)	6.45E-06	3.16E-04	ko05146	GNA15、LAMB4、LAMA1、TLR2、PLCB2、ITGB2、CXCL1、PRKCB、ITGAM、CD14、PIK3CD、RAB7B
免疫系统 (immune system)	血小板激活 (platelet activation)	1.59E-05	6.48E-04	ko04611	LCP2、PTGS1、P2RX1、PLCB2、PIK3R5、FCGR2A、FCER1G、PTGIR、GUCY1A3、SYK、PIK3CD、RASGRP1、PLCG2
感染性疾病 (infectious diseases)	肺结核 (tuberculosis)	3.59E-05	1.16E-03	ko05152	CD74、CORO1A、LSP1、TLR2、FCGR2A、FCGR1A、PLA2R1、FCER1G、ITGB2、CTSS、SYK、ITGAM、CD14、TLR1、CR1、HLA-DOA、HLA-DRA、MRC1
免疫系统 (immune system)	FcγR 介导的吞噬作用 (Fc gamma R-mediated phagocytosis)	2.01E-04	2.07E-04	ko04666	WAS、PTPRC、HCK、DOCK2、BIN1、FCGR2A、FCGR1A、PLPP3、SYK、PRKCB、PIK3CD、PLCG2
生长发育 (development)	破骨细胞分化 (osteoclast differentiation)	0.000123966	3.37E-03	ko04380	TYROBP、LCP2、SPI1、TREM2、LILRB1、LILRB5、NCF2、FCGR2A、FCGR1A、SYK、PIK3CD、CSF1、PLCG2、LILRA6
感染性疾病 (infectious diseases)	疟疾 (malaria)	0.000277305	6.79E-03	ko05144	ITGAL、COMP、CCL2、CD36、TLR2、ITGB2、CR1

表3

图4

图5

参考文献 47

[1]	Staud F, Karahoda R . Trophoblast: The central unit of fetal growth, protection and programming. Int J Biochem Cell Biol, 2018,105:35-40. doi: 10.1016/j.biocel.2018.09.016 pmid: 30266525
[2]	Moser G, Windsperger K, Pollheimer J, de Sousa Lopes SC, Huppertz B,. Human trophoblast invasion: new and unexpected routes and functions. Histochem Cell Biol, 2018,150(4):361-370. doi: 10.1007/s00418-018-1699-0 pmid: 30046889
[3]	Baines KJ, Renaud SJ . Transcription factors that regulate trophoblast development and function. Prog Mol Biol Transl Sci, 2017,145:39-88. doi: 10.1016/bs.pmbts.2016.12.003 pmid: 28110754
[4]	Harris LK, Jones CJ, Aplin JD . Adhesion molecules in human trophoblast - a review. II. extravillous trophoblast. Placenta, 2009,30(4):299-304. doi: 10.1016/j.placenta.2008.12.003
[5]	Chung TW, Park MJ, Kim HS, Choi HJ, Ha KT . Integrin αVβ3 and αVβ5 are required for leukemia inhibitory factor-mediated the adhesion of trophoblast cells to the endometrial cells. Biochem Biophys Res Commun, 2016,469(4):936-940. doi: 10.1016/j.bbrc.2015.12.103 pmid: 26723254
[6]	Huppertz B . Traditional and new routes of trophoblast invasion and their implications for pregnancy diseases. Int J Mol Sci, 2019,21(1):289. doi: 10.3390/ijms21010289
[7]	Malik A, Pal R, Gupta SK . Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion. PLoS One, 2017,12(5):e0178269. doi: 10.1371/journal.pone.0178269 pmid: 28542650
[8]	Huang ZY, Li SW, Fan W, Ma QH . Transforming growth factor β1 promotes invasion of human JEG-3 trophoblast cells via TGF-β/Smad3 signaling pathway. Oncotarget, 2017,8(20):33560-33570. doi: 10.18632/oncotarget.16826 pmid: 28432277
[9]	Chitu V, Stanley ER . Regulation of embryonic and postnatal development by the CSF-1 receptor. Curr Top Dev Biol, 2017,123:229-275. doi: 10.1016/bs.ctdb.2016.10.004 pmid: 28236968
[10]	Ding JL, Yin TL, Yan NN, Cheng YX, Yang J . FasL on decidual macrophages mediates trophoblast apoptosis: A potential cause of recurrent miscarriage. Int J Mol Med, 2019,43(6):2376-2386. doi: 10.3892/ijmm.2019.4146 pmid: 30942389
[11]	Shaik R, Ramakrishna W . Genes and Co-Expression modules common to drought and bacterial stress responses in arabidopsis and rice. PLoS One, 2013,8(10):e77261. doi: 10.1371/journal.pone.0077261 pmid: 24130868
[12]	Robinson MD, McCarthy DJ, Smyth GK,. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 2010,26(1):139-140. doi: 10.1093/bioinformatics/btp616 pmid: 19910308
[13]	Takeshita A, Kusakabe KT, Hiyama M, Kuniyoshi N, Kondo T, Kano K, Kiso Y, Okada T . Dynamics and reproductive effects of complement factors in the spontaneous abortion model of CBA/J×DBA/2 mice. Immunobiology, 2014,219(5):385-391. doi: 10.1016/j.imbio.2014.01.001
[14]	Huang J, Qin H, Yang YH, Chen XY, Zhang JM, Laird S, Wang CC, Chan TF, Li TC . A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage. Reproduction, 2017,153(6):749-758. doi: 10.1530/REP-16-0574 pmid: 28283674
[15]	Yurdakan G, Ekem TE, Bahadir B, Gun BD, Kuzey GM, Ozdamar SO . Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis. Acta Obstet Gynecol Scand, 2008,87(7):775-782. doi: 10.1080/00016340802177412 pmid: 18607815
[16]	Soylu Karapınar O, Benk Şilfeler D, Dolapçıoğlu K, Keskin Kurt R, Beyazıt A . The effect of molar pregnancies on platelet parameters. J Obstet Gynaecol, 2016,36(7):912-915. doi: 10.1080/01443615.2016.1174823 pmid: 27183899
[17]	Girardi G, Salmon JB . The role of complement in pregnancy and fetal loss. Autoimmunity, 2003,36(1):19-26. doi: 10.1080/0891693031000067322 pmid: 12765467
[18]	Kouser L, Madhukaran SP, Shastri A, Saraon A, Ferluga J, Al-Mozaini M, Kishore U . Emerging and novel functions of complement protein C1q. Front Immunol, 2015,6:317. doi: 10.3389/fimmu.2015.00317 pmid: 26175731
[19]	Liu FL, Zhou J, Zhang W, Wang H . Epigenetic regulation and related diseases during placental development. Hereditas (Beijing), 2017,39(4):263-275.
	刘福林, 周瑾, 张蔚, 汪晖 . 胎盘发育过程中的表观遗传学改变及其相关疾病. 遗传, 2017,39(4):263-275.
[20]	Lai XM, Wang YX . Trophoblastic invasion and its regulatory factors. Chin J Birth Heal Hered, 2007,15(3):1-3.
	赖雪梅, 王应雄 . 滋养层侵袭力及其调控因素. 中国优生与遗传杂志, 2007,15(3):1-3.
[21]	Burton GJ, Jauniaux E . Pathophysiology of placental- derived fetal growth restriction. Am J Obstet Gynecol, 2018,218(2S):S745-S761. doi: 10.1016/j.ajog.2017.11.577 pmid: 29422210
[22]	James-Allan LB, Whitley GS, Leslie K, Wallace A, Cartwright JE . Decidual cell regulation of trophoblast is altered in pregnancies at risk of pre-eclampsia. J Mol Endocrinol, 2018. pmid: 32580159
[23]	Zadrozna M, Nowak B, Marcinek A, Duc J . Villous trophoblast cell turnover in placentas from preterm pregnancy and pregnancy complicated by intrauterine growth restriction (IUGR). Folia Biol (Krakow), 2009,58(1-2):79-83. doi: 10.3409/fb58_1-2.79-83
[24]	Check JH, Aly J, Chang E . Improving the chance of successful implantation-Part I-Embryo attachment to the endometrium and adequate trophoblast invasion. Clin Exp Obstet Gynecol, 2016,43(6):787-791. pmid: 29944223
[25]	Burton GJ, Jauniaux E . The cytotrophoblastic shell and complications of pregnancy. Placenta, 2017,60:134-139. doi: 10.1016/j.placenta.2017.06.007 pmid: 28651899
[26]	Yang WM, Lu ZY, Zhi ZF, Liu LL, Deng LJ, Jiang XL, Pang LH . High-throughput transcriptome-Seq and small RNA-Seq reveal novel functional genes and microRNAs for early embryonic arrest in humans. Gene, 2019,697:19-25. doi: 10.1016/j.gene.2018.12.084 pmid: 30776465
[27]	Pan HT, Ding HG, Fang M, Yu B, Cheng Y, Tan YJ, Fu QQ, Lu BB, Cai HG, Jin X, Xia XQ, Zhang T . Proteomics and bioinformatics analysis of altered protein expression in the placental villous tissue from early recurrent miscarriage patients. Placenta, 2018,61:1-10. doi: 10.1016/j.placenta.2017.11.001 pmid: 29277264
[28]	Atanasova MA, Konova EI, Aleksovska TA, Todorova KN, Georgieva MN, Lukanov TH . Anti-fibrillin-1 autoantibodies in normal pregnancy and recurrent pregnancy loss. Autoimmun Rev, 2011,10(3):131-136. doi: 10.1016/j.autrev.2010.09.003
[29]	Vogt L, Schmitz N, Kurrer MO, Bauer M, Hinton HI, Behnke S, Gatto D, Sebbel P, Beerli RR, Sonderegger I, Kopf M, Saudan P, Bachmann MF . VSIG4, a B7 family-related protein, is a negative regulator of T cell activation. J Clin Invest, 2006,116(10):2817-2826. doi: 10.1172/JCI25673 pmid: 17016562
[30]	Helmy KY, Katschke KJ, Gorgani NN, Kljavin NM, Elliott JM, Diehl L, Scales SJ, Ghilardi N, van Lookeren Campagne M,. CRIg: A macrophage complement receptor required for phagocytosis of circulating pathogens. Cell, 2006,124(5):915-927. doi: 10.1016/j.cell.2005.12.039 pmid: 16530040
[31]	Kim DD, Miwa T, Kimura Y, Schwendener RA, van Lookeren Campagne M, Song WC,. Deficiency of decay- accelerating factor and complement receptor 1-related gene/protein y on murine platelets leads to complement- dependent clearance by the macrophage phagocytic receptor CRIg. Blood, 2008,112(4):1109-1119. doi: 10.1182/blood-2008-01-134304 pmid: 18524992
[32]	Mascarell L, Airouche S, Berjont N, Gary C, Gueguen C, Fourcad G, Bellier B, Togbe D, Ryffel B, Klatzmann D, Baron-Bodo V, Moingeon P . The regulatory dendritic cell marker C1q is a potent inhibitor of allergic inflammation. Mucosal Immunol, 2016,10(3):695-704. doi: 10.1038/mi.2016.87 pmid: 27731323
[33]	Girardi G . Complement inhibition keeps mothers calm and avoids fetal rejection. Immunol Invest, 2008,37(5):645-659. doi: 10.1080/08820130802191615 pmid: 18716942
[34]	Girardi G, Prohászka Z, Bulla R, Tedesco F, Scherjon S . Complement activation in animal and human pregnancies as a model for immunological recognition. Mol Immunol, 2011,48(14):1621-1630 doi: 10.1016/j.molimm.2011.04.011
[35]	Teirilä L, Heikkinen-Eloranta J, Kotimaa J, Meri S, Lokki AI . Regulation of the complement system and immunological tolerance in pregnancy. Semin Immunol, 2019,45:101337. doi: 10.1016/j.smim.2019.101337 pmid: 31757607
[36]	Sun J, Jin L . Trophinin, tastin, bystin complex binds to embryo initiation. Chin J Birth Heal Hered, 2005,13(5):113-114.
	孙虹, 靳镭 . Trophinin, tastin, bystin复合体与胚胎起始黏附. 中国优生与遗传杂志, 2005,13(5):113-114.
[37]	Oz HS, Ebersole JL, de Villiers WJS,. The macrophage pattern recognition scavenger receptors SR-A and CD36 protect against microbial induced pregnancy loss. Inflamm Res, 2011,60(1):93-97. doi: 10.1007/s00011-010-0241-1
[38]	Silverstein RL, Febbraio M . CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, behavior. SciSignal, 2009, 2(72): re3.
[39]	Abumrad NA, Goldberg IJ . CD36 actions in the heart: Lipids, calcium, inflammation, repair and more? Biochim Biophys Acta, 2016,1861(10):1442-1449. doi: 10.1016/j.bbalip.2016.03.015 pmid: 27004753
[40]	Wang JC, Li YS . CD36 tango in cancer: signaling pathways and functions. Theranostics, 2019,9(17):4893-4908. doi: 10.7150/thno.36037 pmid: 31410189
[41]	Johnson GA, Burghardt RC, Bazer FW, Spencer TE . Osteopontin: Roles in implantation and placentation. Biol Reprod, 2003,69(5):1458-1471. doi: 10.1095/biolreprod.103.020651 pmid: 12890718
[42]	Yu QB, Wang YX . Cell adhesion molecules to the embryo implantatio. Chin J Birth Heal Hered, 2005,13(1):6-8.
	余秋波, 王应雄 . 细胞粘附分子与胚胎着床. 中国优生与遗传杂志, 2005,13(1):6-8.
[43]	Nardo LG, Nikas G, Makrigiannakis A . Molecules in blastocyst implantation. Role of matrix metalloproteinases, cytokines and growth factors. J Reprod Med, 2003,48(3):137-147. pmid: 12698769
[44]	Gonzalez I, Munita R, Agirre E, Dittmer TA, Gysling K, Misteli T, Luco RF . A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature . Nat Struct Mol Biol, 2015,22(5):370-376. doi: 10.1038/nsmb.3005 pmid: 25849144
[45]	Lieberman J . Tapping the RNA world for therapeutics. Nat Struct Mol Biol, 2018,25(5):357-364. doi: 10.1038/s41594-018-0054-4 pmid: 29662218
[46]	Pérez-Palacios R, Fauque P, Teissandier A, Bourc'his D. Deciphering the early mouse embryo transcriptome by Low-Input RNA-Seq. Methods Mol Biol, 2021,2214:189-205. pmid: 32944911
[47]	Svensson V, Natarajan KN, Ly LH, Miragaia RJ, Labalette C, Macaulay IC, Cvejic A, Teichmann SA . Power analysis of single-cell RNA-sequencing experiments. Nat Methods, 2017,14(4):381-387. doi: 10.1038/nmeth.4220 pmid: 28263961

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序号	临床诊断	年龄(岁)	孕产次	孕周(d)	是否可探胎心	β-HCG(mIU/mL)
1	人工流产	24	G2P0⁺¹	42	胎芽不清	-
2	人工流产	34	G4P0⁺³	43	胎芽不清	-
3	人工流产	29	G3P1⁺¹	49	可见胎心搏动	-
4	人工流产	31	G2P1	47	可见胎心搏动	-
5	人工流产	28	-	51	可见胎心搏动	-
6	胚胎停育	30		55	未见胎心	11,951.4
7	胚胎停育	36	G2P1	50	未见胎心	12,612.1
8	胚胎停育	27	G1P0	57	未见胎心	69,220
9	胚胎停育	27	G1P0	80	未见胎心	-
10	胚胎停育	33	G1P0	59	未见胎心	32,594.4

序列	类型	基因名称	上游序列(5?→3?)	下游序列(5?→3?)
1	mRNA	C1QC	ATCCTGGGAAAAATGGCCCC	GAGGACCGCGTTGAATCTGA
2		VSIG4	TCCAGCAGGCAAAGTACCAG	GTTTCTGGACACGGAGCTCA
3		SPP1	GATGACCATGTGGACAGCCA	AACCACACTATCACCTCGGC
4		CD36	GACCGAGGAAGCCACTTTGA	TAAGCAGGTCTCCAACTGGC
5		NCKAP1L	TGTCTTCCACTCCCGAATGC	TGCAGTGGACAAAGTGAGCA
6		FGD2	TGCTACGCATTCCTCACTGG	ATAGAGCACGAGGGGGTCAT
7		LILRB5	ACCCTGCTGTGTCAGTCATG	GTAGGACCTGATTGCGCTGT
8		FOLR2	GCACCACAAGACAAAGCCAG	CAGGTTGGGTGAGCACTCAT
9		DPPA3	CCAGGGTCTCCACAAATGCT	ATTTCCCTGAGGACTGCTGC
10		MX1	TCGGAGGCTACAGGAAGACT	TTTGCGATGTCCACTTCGGA
11	lncRNA	CLRN1-AS1	GAAAGTCTGAAGCCAGGCCT	CTTTGGGCTTGCACAGTCAC
12		AC104809.4	CGTGGGCTCGTCTAAGTGTT	GCACTGAGCTGTTTGCAGTC
13		LINC01136	ACCTCAGAGGCTACCCACAT	AGAAGAAATCCAGGGGCTGC
14		USP27X-AS1	TGCAACCAGAGGAACTGCAA	AGGTGGACCTATGGGCTTCT

早期停育胚胎的滋养层细胞相关基因与特征分析

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

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[2]	屈亮, 李素, 仇华吉. 单细胞RNA测序技术在病毒研究中的应用[J]. 遗传, 2020, 42(3): 269-277.
[3]	郑婷, 甘麦邻, 沈林園, 牛丽莉, 郭宗义, 王金勇, 张顺华, 朱砺. circRNA及其调控动物骨骼肌发育研究进展[J]. 遗传, 2020, 42(12): 1178-1191.
[4]	禹奇超,宋彬,邹轩轩,王岭,刘德权,李波,马昆. 乳腺癌癌旁组织特异性表达基因分析[J]. 遗传, 2019, 41(7): 625-633.
[5]	刘玄石, 李巍. 早产相关基因的挖掘与特征分析[J]. 遗传, 2019, 41(5): 413-421.
[6]	石田培,张莉. 全转录组学在畜牧业中的应用[J]. 遗传, 2019, 41(3): 193-205.
[7]	赵小蕾, 左晓宇, 覃继恒, 梁岩, 张乃尊, 栾奕昭, 饶绍奇. 基于蛋白质互作知识的生物学通路扩充新方法[J]. 遗传, 2014, 36(4): 387-394.
[8]	郭昊，朱云平，李栋，贺福初. 肿瘤相关生物学通路的发现和建模[J]. 遗传, 2011, 33(8): 809-819.