KBM-7细胞

KBM-7 (KBM-7 cells) 是一种常用于生物医学研究的近单倍体人类慢性粒细胞性白血病 (CGL) 细胞系^[1]，最近初是分离自一个正处于急性期的39岁男性 CGL 患者^[2]。KBM-7细胞跟所有永生的癌细胞系一样可以无限期分裂，然而该细胞系的独特之处在于它除了8号染色体和15号染色体的30兆碱基片段之外^[3]，所有的染色体仅包含一个拷贝^[2]。KBM-7细胞跟其他CML细胞系一样，对带有致癌的BCR-ABL 融合基因的费城染色体呈阳性。

科研用途

KBM-7细胞经过重新编程后，可以产生8号染色体仅有一个拷贝的HAP1细胞系^[4]。HAP1细胞不仅呈现纤维细胞样形态，并且更加接近单倍体，然而HAPl细胞对于维持它们的近单倍体核型不如KBM-7细胞稳定，更加容易转变成二倍体状态。通过切除在HAP1细胞中保留其二倍性的15号染色体的部分后，则可获得真正的单倍体人类细胞HAP2。此外，KBM-7细胞可通过0CT4、Sox2、KLF4和MYC（英语：Myc）的过表达，被重新编程为诱导性多能干细胞 (iPSC)，然而KBM-7衍生的iPSC在去分化程序时，失去原有的近单倍体核型^[5]。

该细胞系最初被认为可以促进将体细胞遗传学应用到哺乳动物细胞生物学的研究^[1]，然而近十年后才由怀特黑德生物医学研究所（英语：Whitehead Institute）成功地将KBM-7细胞应用于人类细胞的基因实验^[6]，后来更成为新型药物的测试模型^[7]。有研究利用KBM-7细胞进行了正向遗传筛选，发现功能未知的MARVEL结构域蛋白蛋白脂质蛋白2是卡波西氏肉瘤疱疹病毒（英语：Kaposi's sarcoma-associated herpesvirus）基因产物K5发挥病毒E3泛素连接酶活性所必需的^[8]。KBM-7细胞可以在悬浊液中生长，并且可以在补充了10％胎牛血清的IMDM培养基中保存，细胞处于亚稳定状态，然而维持近单倍体状态若干个月的KBM-7细胞最终会转变成二倍体^[1]。

衍生细胞系

HAP1细胞
KBM-7/B5细胞

参考资料

^ ^1.0 ^1.1 ^1.2 Kotecki, M; Reddy, PS; Cochran, BH. Isolation and characterization of a near-haploid human cell line.. Experimental cell research. 1999-11-01, 252 (2): 273–80 [2019-12-01]. PMID 10527618. doi:10.1006/excr.1999.4656.
^ ^2.0 ^2.1 Andersson, BS; Beran, M; Pathak, S; Goodacre, A; Barlogie, B; McCredie, KB. Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern.. Cancer genetics and cytogenetics. 1987-02, 24 (2): 335–43 [2019-12-01]. PMID 3466682. doi:10.1016/0165-4608(87)90116-6.
^ Bürckstümmer, T; Banning, C; Hainzl, P; Schobesberger, R; Kerzendorfer, C; Pauler, FM; Chen, D; Them, N; Schischlik, F; Rebsamen, M; Smida, M; Fece de la Cruz, F; Lapao, A; Liszt, M; Eizinger, B; Guenzl, PM; Blomen, VA; Konopka, T; Gapp, B; Parapatics, K; Maier, B; Stöckl, J; Fischl, W; Salic, S; Taba Casari, MR; Knapp, S; Bennett, KL; Bock, C; Colinge, J; Kralovics, R; Ammerer, G; Casari, G; Brummelkamp, TR; Superti-Furga, G; Nijman, SM. A reversible gene trap collection empowers haploid genetics in human cells.. Nature methods. 2013-10, 10 (10): 965–71 [2019-12-01]. PMID 24161985. doi:10.1038/nmeth.2609.
^ Carette, JE; Raaben, M; Wong, AC; Herbert, AS; Obernosterer, G; Mulherkar, N; Kuehne, AI; Kranzusch, PJ; Griffin, AM; Ruthel, G; Dal Cin, P; Dye, JM; Whelan, SP; Chandran, K; Brummelkamp, TR. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.. Nature. 2011-08-24, 477 (7364): 340–3 [2019-12-01]. PMID 21866103. doi:10.1038/nature10348.
^ Carette, JE; Pruszak, J; Varadarajan, M; Blomen, VA; Gokhale, S; Camargo, FD; Wernig, M; Jaenisch, R; Brummelkamp, TR. Generation of iPSCs from cultured human malignant cells.. Blood. 2010-05-20, 115 (20): 4039–42 [2019-12-01]. PMID 20233975. doi:10.1182/blood-2009-07-231845.
^ Carette, JE; Guimaraes, CP; Varadarajan, M; Park, AS; Wuethrich, I; Godarova, A; Kotecki, M; Cochran, BH; Spooner, E; Ploegh, HL; Brummelkamp, TR. Haploid genetic screens in human cells identify host factors used by pathogens.. Science (New York, N.Y.). 2009-11-27, 326 (5957): 1231–5 [2019-12-01]. PMID 19965467. doi:10.1126/science.1178955. （原始内容存档于2013-12-22）.
^ Essletzbichler, P; Konopka, T; Santoro, F; Chen, D; Gapp, BV; Kralovics, R; Brummelkamp, TR; Nijman, SM; Bürckstümmer, T. Megabase-scale deletion using CRISPR/Cas9 to generate a fully haploid human cell line.. Genome research. 2014-12, 24 (12): 2059–65 [2019-12-01]. PMID 25373145. doi:10.1101/gr.177220.114.
^ Timms, RT; Duncan, LM; Tchasovnikarova, IA; Antrobus, R; Smith, DL; Dougan, G; Weekes, MP; Lehner, PJ. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.. PLoS pathogens. 2013, 9 (11): e1003772 [2019-12-01]. PMID 24278019. doi:10.1371/journal.ppat.1003772.

外部链接

Cellosaurus entry for KBM-7 （页面存档备份，存于互联网档案馆）

[b-1] 1.0 ^1.1 ^1.2 Kotecki, M; Reddy, PS; Cochran, BH. Isolation and characterization of a near-haploid human cell line.. Experimental cell research. 1999-11-01, 252 (2): 273–80 [2019-12-01]. PMID 10527618. doi:10.1006/excr.1999.4656.

[a-2] 2.0 ^2.1 Andersson, BS; Beran, M; Pathak, S; Goodacre, A; Barlogie, B; McCredie, KB. Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern.. Cancer genetics and cytogenetics. 1987-02, 24 (2): 335–43 [2019-12-01]. PMID 3466682. doi:10.1016/0165-4608(87)90116-6.

[3] Bürckstümmer, T; Banning, C; Hainzl, P; Schobesberger, R; Kerzendorfer, C; Pauler, FM; Chen, D; Them, N; Schischlik, F; Rebsamen, M; Smida, M; Fece de la Cruz, F; Lapao, A; Liszt, M; Eizinger, B; Guenzl, PM; Blomen, VA; Konopka, T; Gapp, B; Parapatics, K; Maier, B; Stöckl, J; Fischl, W; Salic, S; Taba Casari, MR; Knapp, S; Bennett, KL; Bock, C; Colinge, J; Kralovics, R; Ammerer, G; Casari, G; Brummelkamp, TR; Superti-Furga, G; Nijman, SM. A reversible gene trap collection empowers haploid genetics in human cells.. Nature methods. 2013-10, 10 (10): 965–71 [2019-12-01]. PMID 24161985. doi:10.1038/nmeth.2609.

[c-4] Carette, JE; Raaben, M; Wong, AC; Herbert, AS; Obernosterer, G; Mulherkar, N; Kuehne, AI; Kranzusch, PJ; Griffin, AM; Ruthel, G; Dal Cin, P; Dye, JM; Whelan, SP; Chandran, K; Brummelkamp, TR. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.. Nature. 2011-08-24, 477 (7364): 340–3 [2019-12-01]. PMID 21866103. doi:10.1038/nature10348.

[5] Carette, JE; Pruszak, J; Varadarajan, M; Blomen, VA; Gokhale, S; Camargo, FD; Wernig, M; Jaenisch, R; Brummelkamp, TR. Generation of iPSCs from cultured human malignant cells.. Blood. 2010-05-20, 115 (20): 4039–42 [2019-12-01]. PMID 20233975. doi:10.1182/blood-2009-07-231845.

[6] Carette, JE; Guimaraes, CP; Varadarajan, M; Park, AS; Wuethrich, I; Godarova, A; Kotecki, M; Cochran, BH; Spooner, E; Ploegh, HL; Brummelkamp, TR. Haploid genetic screens in human cells identify host factors used by pathogens.. Science (New York, N.Y.). 2009-11-27, 326 (5957): 1231–5 [2019-12-01]. PMID 19965467. doi:10.1126/science.1178955. （原始内容存档于2013-12-22）.

[7] Essletzbichler, P; Konopka, T; Santoro, F; Chen, D; Gapp, BV; Kralovics, R; Brummelkamp, TR; Nijman, SM; Bürckstümmer, T. Megabase-scale deletion using CRISPR/Cas9 to generate a fully haploid human cell line.. Genome research. 2014-12, 24 (12): 2059–65 [2019-12-01]. PMID 25373145. doi:10.1101/gr.177220.114.

[8] Timms, RT; Duncan, LM; Tchasovnikarova, IA; Antrobus, R; Smith, DL; Dougan, G; Weekes, MP; Lehner, PJ. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.. PLoS pathogens. 2013, 9 (11): e1003772 [2019-12-01]. PMID 24278019. doi:10.1371/journal.ppat.1003772.

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