多能干细胞维持遗传物质稳定性的研究进展

doi:10.6040/j.issn.1671-7554.0.2017.1296

摘要/Abstract

摘要： 由于功能特殊,干细胞不仅是发育生物学研究的重要模型,也在再生医学中有巨大的应用前景。但多能干细胞基因组稳定性是其得以应用的前提。相对于其他多种类型的分化细胞,多能干细胞有着独特的基因组稳定性维持能力和机制,其DNA损伤反应更加复杂也更加强大,但目前对多能干细胞如何高效维持基因组稳定性的机制仍知之甚少,有待进一步探索。简要综述近年在多能干细胞基因组稳定性调控上的研究进展。

关键词: 遗传物质稳定性, 多能干细胞, DNA损伤反应, DNA 复制压力反应

Abstract: Pluripotent stem cells(PSCs)are widely used as models in the field of developmental biology, and have great application prospects in cell-based regenerative medicine. Genomic stability is prerequisite for the clinical applications of PSCs. Compared to other differentiated cells, PSCs have unique features and higher ability in maintaining genomic stability with more complex DNA damage response. However, the underlying molecular mechanisms are still unknown. In this review, we summarized the current progresses in understanding the pathways and mechanisms how PSCs maintained the genomic stability.

Key words: Genomic stability, Pluripotent stem cell, DNA damage response, DNA replication stress response

中图分类号:

郑萍,张伟道,李竞争. 多能干细胞维持遗传物质稳定性的研究进展[J]. 山东大学学报 (医学版), 2018, 56(4): 28-32.

ZHENG Ping, ZHANG Weidao, LI Jingzheng. Maintaining the genomic stability in pluripotent stem cells: the current progresses[J]. Journal of Shandong University (Health Sciences), 2018, 56(4): 28-32.

参考文献

[1] Cervantes RB, Stringer JR, Shao C, et al. Embryonic stem cells and somatic cells differ in mutation frequency and type[J]. Proc Natl Acad Sci U S A, 2002, 99(6): 3586-3590.
[2] Baker DE, Harrison NJ, Maltby E, et al. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo[J]. Nat Biotechnol, 2007, 25(2): 207-215.
[3] Lefort N, Perrier AL, Laâbi Y, et al. Human embryonic stem cells and genomic instability[J]. Regen Med, 2009, 4(6): 899-909.
[4] Werbowetski-Ogilvie TE, Bossé M, Stewart M, et al. Characterization of human embryonic stem cells with features of neoplastic progression[J]. Nat Biotechnol, 2009, 27(1): 91-97.
[5] Vitale I, Manic G, De Maria R, et al. DNA damage in stem cells[J]. Mol Cell, 2017, 66(3): 306-319.
[6] Oliveira PH, da Silva CL,Cabral JM. Concise review: genomic instability in human stem cells: current status and future challenges[J]. Stem Cells, 2014, 32(11): 2824-2832.
[7] Maillard PV, Ciaudo C, Marchais A, et al. Antiviral RNA interference in mammalian cells[J]. Science, 2013, 342(6155): 235-238.
[8] Wu X, Dao Thi VL, Huang Y, et al. Intrinsic immunity shapes viral resistance of stem cells[J]. Cell, 2018, 172(3): 423-438.
[9] Tichy ED, Stambrook PJ. DNA repair in murine embryonic stem cells and differentiated cells[J] Exp Cell Res, 2008, 314(9): 1929-1936.
[10] Blelloch RH, Hochedlinger K, Yamada Y, et al. Nuclear cloning of embryonal carcinoma cells[J]. Proc Natl Acad Sci U S A, 2004, 101(39): 13985-13990.
[11] Blagosklonny MV, Pardee AB. The restriction point of the cell cycle[J]. Cell Cycle, 2002, 1(2): 103-110.
[12] Filion TM, Qiao M, Ghule PN, et al. Survival responses of human embryonic stem cells to DNA damage[J]. J Cell Physiol, 2009, 220(3): 586-592.
[13] Chuykin IA, Lianguzova MS, Pospelova TV, et al. Activation of DNA damage response signaling in mouse embryonic stem cells[J]. Cell Cycle, 2008, 7(18): 2922-2928.
[14] Tichy ED, Pillai R, Deng L, et al. Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks[J]. Stem Cells Dev, 2010, 19(11): 1699-1711.
[15] Serrano L, Liang L, Chang Y, et al. Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells[J]. Stem Cells Dev, 2011, 20(2): 363-374.
[16] Liu JC, Guan X, Ryan JA, et al. High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis[J]. Cell Stem Cell, 2013, 13(4): 483-491.
[17] Lin T, Chao C, Saito S, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression[J]. Nat Cell Biol, 2005, 7(2): 165-171.
[18] Zhao B, Zhang WD, Duan YL, et al. Filia is an ESC-specific regulator of DNA damage response and safeguards genomic stability[J]. Cell Stem Cell, 2015, 16(6): 684-698.
[19] Xiong J, Todorova D, Su NY, et al. Stemness factor Sall4 is required for DNA damage response in embryonic stem cells[J]. J Cell Biol, 2015, 208(5): 513-520.
[20] Zhao B, Zhang W, Cun Y, et al. Mouse embryonic stem cells have increased capacity for replication fork restart driven by the specific Filia-Floped protein complex[J]. Cell Res, 2018, 28(1): 69-89.
[21] Dumitru R, Gama V, Fagan BM, et al. Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis[J]. Mol Cell, 2012, 46(5): 573-583.
[22] Zalzman M, Falco G, Sharova LV, et al. Zscan4 regulates telomere elongation and genomic stability in ES cells[J]. Nature, 2010, 464(7290): 858-863.
[23] Zeman MK, Cimprich KA. Causes and consequences of replication stress[J]. Nat Cell Biol, 2014, 16(1): 2-9.
[24] Byun TS, Pacek M, Yee MC, et al. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint[J]. Genes Dev, 2005, 19(9): 1040-1052.
[25] Harper JW, Elledge SJ. The DNA damage response: ten years after[J]. Molecular Cell, 2007, 28(5): 739-745.
[26] Bass TE, Luzwick JW, Kavanaugh G, et al. ETAA1 acts at stalled replication forks to maintain genome integrity[J]. Nature Cell Biology, 2016, 18(11): 1185-1195.
[27] Lee YC, Zhou Q, Chen J, et al. RPA-binding protein ETAA1 is an ATR activator involved in DNA replication stress response[J]. Curr Biol, 2016, 26(24): 3257-3268.
[28] Ahuja AK, Jodkowska K, Teloni F, et al. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells[J]. Nat Commun, 2016, 7: 10660.
[29] Savatier P, Lapillonne H, Jirmanova L, et al. Analysis of the cell cycle in mouse embryonic stem cells[J]. Methods Mol Biol, 2002, 185: 27-33.
[30] Sirbu BM, Couch FB, Cortez D. Monitoring the spatiotemporal dynamics of proteins at replication forks and in assembled chromatin using isolation of proteins on nascent DNA[J]. Nat Protoc, 2012, 7(3): 594-605.
[31] Mantel C, Guo Y, Lee MR, et al. Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability[J]. Blood, 2007, 109(10): 4518-4527.
[32] Hong Y, Cervantes RB, Tichy E, et al. Protecting genomic integrity in somatic cells and embryonic stem cells[J]. Mutat Res, 2007, 614(1-2): 48-55.
[33] Gonfloni S. Targeting DNA damage response: threshold, chromatin landscape and beyond[J]. Pharmacol Ther, 2013, 138(1): 46-52.
[34] Lee JH, Paull TT. ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex[J]. Science, 2005, 308(5721): 551-554.
[35] Stambrook PJ, Tichy ED. Preservation of genomic integrity in mouse embryonic stem cells[J]. Adv Exp Med Biol, 2010, 695: 59-75.
[36] Pines A, Kelstrup CD, Vrouwe MG, et al. Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells[J]. Mol Cell Biol, 2011, 31(24): 4964-4977.
[37] Carreras Puigvert J, von Stechow L, Siddappa R, et al. Systems biology approach identifies the kinase csnk1a1 as a regulator of the DNA damage response in embryonic stem cells[J]. Sci Signal, 2013, 6(259): ra5.
[38] Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells[J]. Cell, 2003, 113(5): 643-655.
[39] Lee Y, Katyal S, Downing SM, et al. Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors[J]. Nat Neurosci, 2012, 15(6): 819-826.
[40] McKinnon PJ. Maintaining genome stability in the nervous system[J]. Nat Neurosci, 2013, 16(11): 1523-1529.
[41] Lee Y, Shull ER, Frappart PO, et al. ATR maintains select progenitors during nervous system development[J]. EMBO J, 2012, 31(5): 1177-1189.
[42] Enriquez-Rios V, Dumitrache LC, Downing SM, et al. DNA-PKcs, ATM, and ATR interplay maintains genome integrity during neurogenesis[J]. J Neurosci, 2017, 37(4): 893-905.
[43] Zhou ZW, Tapias A, Bruhn C, et al. DNA damage response in microcephaly development of MCPH1 mouse model[J]. DNA Repair(Amst), 2013, 12(8): 645-655.
[44] Wei PC, Chang AN, Kao J, et al. Long neural genes harbor recurrent DNA break clusters in neural stem/progenitor cells[J]. Cell, 2016, 164(4): 644-655.
[45] Hamatani T, Falco G, Carter MG, et al. Age-associated alteration of gene expression patterns in mouse oocytes[J]. Hum Mol Genet, 2004, 13(19): 2263-2278.
[46] Keefe DL, Liu L. Telomeres and reproductive aging[J]. Reprod Fertil Dev, 2009, 21(1): 10-14.
[47] Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility-a clinicians perspective[J]. Reprod Biomed Online, 2005, 11(5): 641-650.
[48] Suh EK, Yang A, Kettenbach A, et al. p63 protects the female germ line during meiotic arrest[J]. Nature, 2006, 444(7119): 624-628.
[49] Titus S, Li F, Stobezki R, et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans[J]. Sci Transl Med, 2013, 5(172): 172ra21.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed