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不死化ヒト肝細胞を用いたB型肝炎ウイルス（HBV）感染培養系の開発と、これを用いたHBV生活環の解析

赤堀, 祐一 京都大学 DOI:10.14989/doctor.k23341

2021.03.23

概要

B 型肝炎ウイルス（Hepatitis B virus; HBV）は、ヘパドナウイルス科に属する DNAウイルスである。B 型肝炎の原因ウイルスであり、世界中で年間約 90 万人が肝硬変、肝がんなどのHBV 関連疾患で死亡していると推定されている。

近年、HBV 感染受容体として同定されたヒトナトリウム-タウロコール酸共役輸送体（Na+-taurocholate co-transporting polypeptide; NTCP）を用いた HBV 感染培養系の確立により、HBV 生活環のほぼ全ての過程を解析することが可能となった。しかしながら、これまでに確立された HBV 培養系の多くが、正常な肝細胞とは異なる遺伝子発現プロフィールを持つ肝がん由来細胞株を利用していることから、生体内における HBV と宿主細胞間の相互作用の研究には一定の限界があると考えられた。また、生体内の生理的状態の大部分を再現するヒト初代培養肝細胞も、高価であることや分子生物学的手法の導入が困難であること、長期に培養できないといった問題を抱えている。

本研究は、これらの問題を解決するために、不死化ヒト肝細胞である HuS-E/2 細胞に NTCP 発現プラスミドを恒常的に導入した細胞を樹立し、これを用いて新たな HBV感染培養系を確立することを目的として行った。

最終的に、外来性 NTCP の高い発現を示した細胞クローンから E/NtG8 細胞を選択し、Cellbed 担体を用いて立体培養した実験系を構築した。これまでの肝がん由来細胞を用いた HBV 感染培養系は肝がん由来培養細胞に産生させた組換え体 HBV（Cell culture HBV; HBVcc）に高い感染感受性を示すが、血清由来の HBV（Blood-borne HBV; HBVbb）に対する感染感受性は認められなかった。しかしながら、立体培養 E/NtG8 細胞は HBVbb と HBVcc の両方の感染を許容し、特に、HBVbb に対して初代培養ヒト肝細胞と同等の高い感染感受性を持つことがわかった。また、肝がん由来細胞を用いた HBV 感染培養系では HBVcc 感染後に効率の良い HBV 粒子の産生は認められていないが、この立体培養 E/NtG8 細胞からは、HBVbb と同様の高い感染性を持つ HBV 粒子の産生が、HBVbb 感染後から約 1 ヶ月間観察された。これらの結果は、立体培養 E/NtG8 細胞が正常ヒト肝細胞に類似した条件で、HBV 生活環の全てのステップを再現することが可能であることを示唆している。遺伝子発現解析から、この立体培養 E/NtG8 細胞では、平面培養に比較して、肝細胞の成熟化に関連し、HBV 複製を促進することが知られる、肝細胞特異的転写因子 Hepatocyte nuclear factor（HNF）1 αや HNF4αの発現や、HBV 粒子産生に関与することが報告されている脂肪酸合成系酵素の遺伝子発現の亢進が認められ、HBV の効率的な増殖に寄与していることが推定された。一方、HBV に対する宿主制限因子として報告された Structural maintenance of chromosomes 6 (SMC6)の発現は平面培養に比較して減少していた。この結果を元に肝組織内のヒト肝細胞などにおける SMC6 遺伝子発現を検討したところ、同様にその発現は低レベルであり、生体内における制限因子としての機能については再検討する必要があることを見出した。

今後、本研究で確立された HBV 感染培養系は、生理的条件に類似した条件下における HBV と宿主細胞因子間の相互作用に関する新たな発見や、がん化などの HBV 感染による病原性発現メカニズムの解明に貢献することが期待された。

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[1] Summers J, O'Connell A, Millman I. Genome of hepatitis B virus: restriction enzyme cleavage and structure of DNA extracted from Dane particles. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4597-601. doi: 10.1073/pnas.72.11.4597.

[2] Tiollais P, Pourcel C, Dejean A. The hepatitis B virus. Nature. 1985 Oct 10-16;317(6037):489-95. doi: 10.1038/317489a0.

[3] Quarleri J. Core promoter: a critical region where the hepatitis B virus makes decisions. World J Gastroenterol. 2014 Jan 14;20(2):425-35. doi: 10.3748/wjg.v20.i2.425.

[4] Dane DS, Cameron CH, Briggs M. Virus-like particles in serum of patients with Australia-antigen-associated hepatitis. Lancet. Apr 4;1(7649): 695-8. 1970

[5] Schulze A, Gripon P, Urban S. Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. Hepatology. 2007 Dec;46(6):1759-68. doi: 10.1002/hep.21896.

[6] Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13;3. doi: 10.7554/eLife.00049.

[7] Iwamoto M, Saso W, Sugiyama R, Ishii K, Ohki M, Nagamori S, Suzuki R, Aizaki H, Ryo A, Yun JH, Park SY, Ohtani N, Muramatsu M, Iwami S, Tanaka Y, Sureau C, Wakita T, Watashi K. Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization. Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8487-8492. doi: 10.1073/pnas.1811064116. Epub 2019 Apr 5.

[8] Gallucci L, Kann M. Nuclear Import of Hepatitis B Virus Capsids and Genome. Viruses. 2017 Jan 21;9(1):21. doi: 10.3390/v9010021.

[9] Sohn JA, Litwin S, Seeger C. Mechanism for CCC DNA synthesis in hepadnaviruses. PLoS One. 2009 Nov 30;4(11):e8093. doi: 10.1371/journal.pone.0008093.

[10] Petit MA, Pillot J. HBc and HBe antigenicity and DNA-binding activity of major core protein P22 in hepatitis B virus core particles isolated from the cytoplasm of human liver cells. J Virol. 1985 Feb;53(2):543-51. doi:10.1128/JVI.53.2.543-551.1985.

[11] Stibbe W, Gerlich WH. Structural relationships between minor and major proteins of hepatitis B surface antigen. J Virol. 1983 May;46(2):626-8. doi: 10.1128/JVI.46.2.626-628.1983.

[12] Heermann KH, Goldmann U, Schwartz W, Seyffarth T, Baumgarten H, Gerlich WH. Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984 Nov;52(2):396-402. doi: 10.1128/JVI.52.2.396-402.1984.

[13] Moriarty AM, Alexander H, Lerner RA, Thornton GB. Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma. Science. 1985 Jan 25;227(4685):429-33. doi: 10.1126/science.2981434.

[14] Bartenschlager R, Schaller H. Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome. EMBO J. 1992 Sep;11(9):3413-20.

[15] Summers J, Mason WS. Replication of the genome of a hepatitis B--like virus by reverse transcription of an RNA intermediate. Cell. 1982 Jun;29(2):403-15. doi: 10.1016/0092-8674(82)90157-x.

[16] Will H, Reiser W, Weimer T, Pfaff E, Büscher M, Sprengel R, Cattaneo R, Schaller H. Replication strategy of human hepatitis B virus. J Virol. 1987 Mar;61(3):904-11. doi: 10.1128/JVI.61.3.904-911.1987.

[17] Köck J, Rösler C, Zhang JJ, Blum HE, Nassal M, Thoma C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog. 2010 Sep 2;6(9):e1001082. doi: 10.1371/journal.ppat.1001082.

[18] Seifer M, Hamatake RK, Colonno RJ, Standring DN. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob Agents Chemother. 1998 Dec;42(12):3200-8. doi: 10.1128/AAC.42.12.3200.

[19] Ying C, De Clercq E, Neyts J. Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture. J Viral Hepat. 2000 Jan;7(1):79-83. doi: 10.1046/j.1365-2893.2000.00192.x.

[20] European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20.

[21] Hayashi Y, Koike K. Interferon inhibits hepatitis B virus replication in a stable expression system of transfected viral DNA. J Virol. 1989 Jul;63(7):2936-40. doi: 10.1128/JVI.63.7.2936-2940.1989.

[22] Belloni L, Allweiss L, Guerrieri F, Pediconi N, Volz T, Pollicino T, Petersen J, Raimondo G, Dandri M, Levrero M. IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest. 2012 Feb;122(2):529-37. doi: 10.1172/JCI58847. Epub 2012 Jan 17.

[23] Tsuge M, Uchida T, Hiraga N, Kan H, Makokha GN, Abe-Chayama H, Miki D, Imamura M, Ochi H, Hayes CN, Shimozono R, Iwamura T, Narumi H, Suzuki T, Kainoh M, Taniguchi T, Chayama K. Development of a Novel Site-Specific Pegylated Interferon Beta for Antiviral Therapy of Chronic Hepatitis B Virus. Antimicrob Agents Chemother. 2017 May 24;61(6):e00183-17. doi: 10.1128/AAC.00183-17. Print 2017 Jun.

[24] Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, Sprinzl MF, Koppensteiner H, Makowska Z, Volz T, Remouchamps C, Chou WM, Thasler WE, Hüser N, Durantel D, Liang TJ, Münk C, Heim MH, Browning JL, Dejardin E, Dandri M, Schindler M, Heikenwalder M, Protzer U. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014 Mar 14;343(6176):1221-8. doi: 10.1126/science.1243462. Epub 2014 Feb 20.

[25] Tsurimoto T, Fujiyama A, Matsubara K. Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. Proc Natl Acad Sci U S A. 1987 Jan;84(2):444-8. doi: 10.1073/pnas.84.2.444.

[26] Yaginuma K, Shirakata Y, Kobayashi M, Koike K. Hepatitis B virus (HBV) particles are produced in a cell culture system by transient expression of transfected HBV DNA. Proc Natl Acad Sci U S A. 1987 May;84(9):2678-82. doi: 10.1073/pnas.84.9.2678.

[27] Sells MA, Chen ML, Acs G. Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1005-9. doi: 10.1073/pnas.84.4.1005.

[28] Ladner SK, Otto MJ, Barker CS, Zaifert K, Wang GH, Guo JT, Seeger C, King RW. Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication. Antimicrob Agents Chemother. 1997 Aug;41(8):1715-20. doi: 10.1128/AAC.41.8.1715.

[29] Bchini R, Capel F, Dauguet C, Dubanchet S, Petit MA. In vitro infection of human hepatoma (HepG2) cells with hepatitis B virus. J Virol. 1990 Jun;64(6):3025-32. doi: 10.1128/JVI.64.6.3025-3032.1990.

[30] Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, Van De Rijn M, Botstein D, Brown PO. Gene expression patterns in human liver cancers. Mol Biol Cell. 2002; 13: 1929-1939.

[31] Costantini S, Di Bernardo G, Cammarota M, Castello G, Colonna G. Gene expression signature of human HepG2 cell line. Gene. 2013; 518: 335-345.

[32] Tnani M, Bayard BA. Evidence for IRF-1-dependent gene expression deficiency in interferon unresponsive HepG2 cells. Biochim Biophys Acta. 1999; 1451: 59-72.

[33] Li K, Chen Z, Kato N, Gale M Jr, Lemon SM. Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. J Biol Chem. 2005; 280: 16739-16747.

[34] Tsugawa Y, Kato H, Fujita T, Shimotohno K, Hijikata M. Critical role of interferon-α constitutively produced in human hepatocytes in response to RNA virus infection. PLoS One. 2014; 9: e89869. doi: 10.1371/journal.pone.0089869.

[35] Gripon P, Diot C, Thézé N, Fourel I, Loreal O, Brechot C, Guguen-Guillouzo C. Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide. J Virol. 1988 Nov;62(11):4136-43. doi: 10.1128/JVI.62.11.4136-4143.1988.

[36] Galle PR, Hagelstein J, Kommerell B, Volkmann M, Schranz P, Zentgraf H. In vitro experimental infection of primary human hepatocytes with hepatitis B virus. Gastroenterology. 1994 Mar;106(3):664-73. doi: 10.1016/0016-5085(94)90700-5.

[37] Aly HH, Qi Y, Atsuzawa K, Usuda N, Takada Y, Mizokami M, Shimotohno K, Hijikata M. Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus. Hepatology. 2009 Sep;50(3):689-96. doi: 10.1002/hep.23034.

[38] Huang HC, Chen CC, Chang WC, Tao MH, Huang C. Entry of hepatitis B virus into immortalized human primary hepatocytes by clathrin-dependent endocytosis. J Virol. 2012 Sep;86(17):9443-53. doi: 10.1128/JVI.00873-12. Epub 2012 Jun 27.

[39] Yao WL, Ikeda S, Tsukamoto Y, Shindo K, Otakaki Y, Qin M, Iwasawa Y, Takeuchi F, Kaname Y, Chou YC, Chang C, Watashi K, Wakita T, Noda T, Kato H, Fujita T. Establishment of a human hepatocellular cell line capable of maintaining long-term replication of hepatitis B virus. Int Immunol. 2017 Mar 1;29(3):109-120. doi: 10.1093/intimm/dxx012.

[40] Ishida Y, Yamasaki C, Yanagi A, Yoshizane Y, Fujikawa K, Watashi K, Abe H, Wakita T, Hayes CN, Chayama K, Tateno C. Novel robust in vitro hepatitis B virus infection model using fresh human hepatocytes isolated from humanized mice. Am J Pathol. 2015 May;185(5):1275-85. doi: 10.1016/j.ajpath.2015.01.028. Epub 2015 Mar 17.

[41] Ogura N, Watashi K, Noguchi T, Wakita T. Formation of covalently closed circular DNA in Hep38.7-Tet cells, a tetracycline inducible hepatitis B virus expression cell line. Biochem Biophys Res Commun. 2014 Sep 26;452(3):315-21. doi: 10.1016/j.bbrc.2014.08.029. Epub 2014 Aug 20.

[42] Iwamoto M, Watashi K, Tsukuda S, Aly HH, Fukasawa M, Fujimoto A, Suzuki R, Aizaki H, Ito T, Koiwai O, Kusuhara H, Wakita T. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem Biophys Res Commun. 2014 Jan 17;443(3):808-13. doi: 10.1016/j.bbrc.2013.12.052. Epub 2013 Dec 14.

[43] Lenhoff RJ, Summers J. Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. J Virol. 1994 Jul;68(7):4565-71. doi: 10.1128/JVI.68.7.4565-4571.1994.

[44] Sugiyama M, Tanaka Y, Kato T, Orito E, Ito K, Acharya SK, Gish RG, Kramvis A, Shimada T, Izumi N, Kaito M, Miyakawa Y, Mizokami M. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology. 2006; 44: 915-924.

[45] Qu B, Ni Y, Lempp FA, Vondran FWR, Urban S. T5 Exonuclease Hydrolysis of Hepatitis B Virus Replicative Intermediates Allows Reliable Quantification and Fast Drug Efficacy Testing of Covalently Closed Circular DNA by PCR. J Virol. 2018 Nov 12;92(23):e01117-18. doi: 10.1128/JVI.01117-18. Print 2018 Dec 1.

[46] Hagenbuch B, Meier PJ. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. J Clin Invest. 1994 Mar;93(3):1326-31. doi: 10.1172/JCI117091.

[47] Appelman MD, Chakraborty A, Protzer U, McKeating JA, van de Graaf SF. N-Glycosylation of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) Determines Its Trafficking and Stability and Is Required for Hepatitis B Virus Infection. PLoS One. 2017 Jan 26;12(1):e0170419. doi: 10.1371/journal.pone.0170419. eCollection 2017.

[48] Decorsière A, Mueller H, van Breugel PC, Abdul F, Gerossier L, Beran RK, Livingston CM, Niu C, Fletcher SP, Hantz O, Strubin M. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature. 2016 Mar 17;531(7594):386-9. doi: 10.1038/nature17170.

[49] Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M, Zoulim F, Hantz O, Protzer U. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. J Hepatol. 2011 Nov;55(5):996-1003. doi: 10.1016/j.jhep.2011.02.015. Epub 2011 Mar 2.

[50] van Breugel PC, Robert EI, Mueller H, Decorsière A, Zoulim F, Hantz O, Strubin M. Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal DNA templates. Hepatology. 2012 Dec;56(6):2116-24. doi: 10.1002/hep.25928. Epub 2012 Sep 24.

[51] Miyakawa Y, Mizokami M. Classifying hepatitis B virus genotypes. Intervirology. 2003;46(6):329-38. doi: 10.1159/000074988.

[52] Hong R, Bai W, Zhai J, Liu W, Li X, Zhang J, Cui X, Zhao X, Ye X, Deng Q, Tiollais P, Wen Y, Liu J, Xie Y. Novel recombinant hepatitis B virus vectors efficiently deliver protein and RNA encoding genes into primary hepatocytes. J Virol. 2013 Jun;87(12):6615-24. doi: 10.1128/JVI.03328-12. Epub 2013 Apr 3.

[53] Zheng Y, Li J, Ou JH. Regulation of hepatitis B virus core promoter by transcription factors HNF1 and HNF4 and the viral X protein. J Virol. 2004; 78: 6908-6914.

[54] Okamura H, Nio Y, Akahori Y, Kim S, Watashi K, Wakita T, Hijikata M. Fatty acid biosynthesis is involved in the production of hepatitis B virus particles. Biochem Biophys Res Commun. 2016; 475: 87-92.

[55] Lazar C, Durantel D, Macovei A, Zitzmann N, Zoulim F, Dwek RA, Branza-Nichita N. Treatment of hepatitis B virus-infected cells with alpha-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity. Antiviral Res. 2007; 76: 30-37.

[56] Lambert C, Döring T, Prange R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J Virol. 2007; 81: 9050-9060.

[57] Yan R, Zhao X, Cai D, Liu Y, Block TM, Guo JT, Guo H. J Virol. The interferon-inducible protein tetherin inhibits hepatitis B virus virion secretion. 2015; 89: 9200-9212.

[58] Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, Guguen-Guillouzo C. Infection of a human hepatoma cell line by hepatitis B virus. Proc Natl Acad Sci U S A. 2002 Nov 26;99

[59] Kaneko S, Kakinuma S, Asahina Y, Kamiya A, Miyoshi M, Tsunoda T, Nitta S, Asano Y, Nagata H, Otani S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Nakauchi H, Nishitsuji H, Ujino S, Shimotohno K, Iwamoto M, Watashi K, Wakita T, Watanabe M. Human induced pluripotent stem cell-derived hepatic cell lines as a new model for host interaction with hepatitis B virus. Sci Rep. 2016; 6: 29358. doi: 10.1038/srep29358.

[60] Sakurai F, Mitani S, Yamamoto T, Takayama K, Tachibana M, Watashi K, Wakita T, Iijima S, Tanaka Y, Mizuguchi H. Human induced-pluripotent stem cell-derived hepatocyte-like cells as an in vitro model of human hepatitis B virus infection. Sci Rep. 2017; 7: 45698. doi: 10.1038/srep45698.

[61] Murayama A, Yamada N, Osaki Y, Shiina M, Aly HH, Iwamoto M, Tsukuda S, Watashi K, Matsuda M, Suzuki R, Tanaka T, Moriishi K, Suzuki T, Nishitsuji H, Sugiyama M, Mizokami M, Shimotohno K, Wakita T, Muramatsu M, Liang TJ, Kato T. N-Terminal PreS1 Sequence Regulates Efficient Infection of Cell-Culture-Generated Hepatitis B Virus. Hepatology. 2020 May 23. doi: 10.1002/hep.31308. Online ahead of print.

[62] König A, Yang J, Jo E, Park KHP, Kim H, Than TT, Song X, Qi X, Dai X, Park S, Shum D, Ryu WS, Kim JH, Yoon SK, Park JY, Ahn SH, Han KH, Gerlich WH, Windisch MP. Efficient long-term amplification of hepatitis B virus isolates after infection of slow proliferating HepG2-NTCP cells. J Hepatol. 2019 Aug;71(2):289-300. doi: 10.1016/j.jhep.2019.04.010. Epub 2019 May 8.

[63] Neil SJ, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008 Jan 24;451(7177):425-30. doi: 10.1038/nature06553. Epub 2008 Jan 16.

[64] Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008 Apr 17;3(4):245-52. doi: 10.1016/j.chom.2008.03.001. Epub 2008 Mar 13.

[65] Dafa-Berger A, Kuzmina A, Fassler M, Yitzhak-Asraf H, Shemer-Avni Y, Taube R. Modulation of hepatitis C virus release by the interferon-induced protein BST-2/tetherin.Virology. 2012 Jul 5;428(2):98-111. doi:10.1016/j.virol.2012.03.011. Epub 2012 Apr 20.

[66] Verver DE, van Pelt AM, Repping S, Hamer G. Role for rodent Smc6 in pericentromeric heterochromatin domains during spermatogonial differentiation and meiosis. Cell Death Dis. 2013 Aug 1;4(8):e749. doi: 10.1038/cddis.2013.269.

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