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个人概况：
刘林，博士，南开大学教授。教育部“长江学者”奖励计划特聘教授，国家杰出青年基金获得者, 国家百千万人才工程“有突出贡献中青年专家”。1993年北京农业大学获博士学位。1994-1998年先后曾赴英国剑桥Babraham研究所、美国康奈尔大学、康州大学作访问学者、博士后研究。1998-2004年美国布朗大学医学院、妇女儿童医院妇产科系研究员、助理教授。2004年中山大学特聘教授。2007年南开大学生命科学学院特聘教授。2006-2011兼聘南佛罗里达大学医学院妇产科系访问助理教授。1998-2011美国海洋生物学实验室（MBL）兼职副研究员。现主要研究方向：1) 端粒和异染色质在多能性干细胞多能性及在体细胞重编程、肿瘤发生和复发中的作用及调节机制; 2) 卵巢衰老机制及抗卵巢衰老的新策略。 主持了多项国家重大项目，包括国家重点研发计划、国家重大科学研究计划、国家国际科技合作专项、国家自然科学基金委重点及重大研究计划项目，及天津市“干细胞与再生医学”创新团队带头人等。担任多个国际科技期刊审稿人和编委包括Science Bulletin, Signal Transduction and Targeted Therapy, Frontiers in Oncology, J Assist Reprod Genet等。发表SCI论文150余篇。
Personal profile：
Lin Liu received Doctorate degree in 1993 in Reproductive Biology and Biotechnology from Beijing Agricultural University (now China Agricultural University). He was a visiting scholar at the BBSRC Babraham Institute, Cambridge, UK, 1994-1996 and then did two year post-doctorate training in Cornell University and University of Connecticut, USA, 1996-1998. He worked as an Investigator and Assistant Professor at Women & Infants Hospital/Brown Medical School, 1998-2004. He was Professor at Sun Yat-sen University, Guangzhou, 2004-2007, and currently is Professor in Nankai University, since 2007. He was Adjunct Assistant Scientist at Marine Biological Laboratory, 1998-2009, Visiting Faculty at the University of South Florida College of Medicine, New York University Langone Medical Center, and Member of H Lee Moffitt Cancer Center & Research Institute. He has been interested in reproductive aging and egg senescence, molecular mechanisms underlying early embryo development and differentiation, telomere biology, and derivation and understanding biology of patient-specific stem cells (e.g. parthenogenetic and induced pluripotent stem cells) that might be useful for regenerative medicine, particularly for treatment of reproductive aging and associated diseases. Dr. Liu has served as editorial board of several journals in biology and reproductive biology, Served as a reviewer and editorial board member of many international scientific journals, including Science Bulletin, Signal Transduction and Targeted Therapy, Frontiers in Oncology, J Assist Reprod Genet, etc. and received prominent awards, including Outstanding Youth Foundation of China National Natural Science Foundation in 2005 and Changjiang Scholar Program Professor appointed by Ministry of Education of China in 2003. He has published over 150 papers in the related fields in peer reviewed international journals, including prestigious Nat Cell Biol, Nat Biotech, Nature, Dev Cell, Cell Rep, Cell Res, PNAS, Hum Mol Gen, Stem Cells, Hum Reprod etc.
Research Fields：1) The role and regulatory mechanism of telomeres and heterochromatin in the pluripotency of pluripotent stem cells and in somatic cell reprogramming, tumorigenesis and recurrence; 2) The mechanism of ovarian aging and new strategies for anti-ovarian aging.
招生方向：干细胞与发育生物学
Enrollment Direction: Stem Cells and Developmental Biology
叶孝颖 巩陶婉 杨姣 李念念 赵楠楠 王海滢 刘林林 石盼盼 衡黛 刘纯 赵爽 冯国锋 李杰 刘畅 尹国兴 于永芹 金开让 陈吉玉 李卉玉 武艺葳
2020年毕业合照留念
2018年毕业合照留念
2017年毕业合照留念
2016年毕业合照留念
2015年毕业合照留念
2014年毕业合照留念
1. 国家重点研发计划项目 端粒调控反转座子活性与干细胞多能性的分子机制
2. 国家重点研发计划项目 线粒体遗传疾病治疗的辅助生殖新技术研究
3. 国家自然科学基金重点项目 胚胎性腺体细胞调控减数分裂启动和进程的分子机制
4. 天津市科学技术局重点项目 人胚胎干细胞多能性状态 (naive vs primed) 影响分化能力的染色质高级结构调控机制
1. 饲养层细胞调控小鼠胚胎干细胞端粒稳态和多能性维持的作用和机制。
首次阐明饲养层细胞通过分泌BMP4、Fstl1激活多能干细胞中2-cell胚胎期基因的表达，维持多能干细胞的端粒长度、基因组稳定和多向发育潜能；饲养层细胞可以维持胚胎干细胞体外长期培养过程中的染色体稳定，人胚胎干细胞培养多使用无饲养层细胞的条件，在长期传代过程中可能会导致染色体不稳定，限制其临床应用。该研究强调了染色体稳定在多能干细胞体外长期扩增中的关键作用，为干细胞安全地应用于临床提供理论支持。
2. 利用化学重编程将卵巢颗粒细胞转变为卵子并获健康小鼠。
通过完全化学小分子的方法，成功将卵巢颗粒细胞重编程为具有生殖系转移能力的诱导性多能干细胞，进而分化为卵子，并通过正常受精获得健康小鼠。该突破属世界首次，为保持生育能力、调节机体内分泌等研究开辟了新思路。这种化学重编程的方法能够有效避免伦理问题，降低安全风险。
3. 利用整合单细胞技术揭秘了结直肠癌的肿瘤干细胞不同状态和特异分子特征。
肿瘤干细胞是导致结直肠癌患者治疗后复发的潜在元凶。通过单细胞转录组整合端粒长度检测技术研究发现结直肠癌肿瘤干细胞处于静息状态且具有相对短的端粒长度，在特定条件下又可以转变为快速增长且端粒获得延长的肿瘤细胞，这些静息态的肿瘤干细胞可能是导致肿瘤复发和耐药的根本原因。传统的肿瘤治疗虽然可以很好的杀伤处于增殖状态的肿瘤细胞，但静息态的肿瘤干细胞有可能产生耐药性。同样，端粒酶抑制药物也只能对增殖中的端粒酶阳性的肿瘤细胞起作用，而不能对端粒短、端粒酶活性低，其处于静息状态的肿瘤干细胞起到靶向的效果。这些发现将为优化肿瘤治疗策略，联合靶向肿瘤干细胞并缓解肿瘤耐药作用提供有益参考。
Hua Wang, Peng Gong, Tong Chen, Shan Gao, Zhenfeng Wu, Xiaodong Wang, Jie Li, Sadie L. Marjani, José Costa, Sherman M. Weissman*, Feng Qi*, Xinghua Pan*, and Lin Liu*. Colorectal Cancer Stem Cell States Uncovered by Simultaneous Single-Cell Analysis of Transcriptome and Telomeres. Adv. Sci. 2004320 (2021).
Dai Heng, Xiaoyan Sheng, Chenglei Tian, Jie Li, Linlin Liu, Mo Gou, Lin Liu*. Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice. Aging Cell 20(2): e13304 (2021).
Huasong Wang, Linlin Liu, Mo Gou, Guian Huang, Chenglei Tian, Jiao Yang, Haiying Wang, Qin Xu, Guo Liang Xu, Lin Liu*. Roles of Tet2 in meiosis, fertility and reproductive aging. Protein Cell 20. doi: 10.1007/s13238-020-00805-8 (2020).
Tian C, Liu L, Ye X, Fu H, Sheng X, Wang L, Wang H, Heng D, and Liu L*. Functional Oocytes Derived from Granulosa Cells. Cell Reports 29(13):4256 (2019).
Zhang W, Chen F, Chen R, Xie D, Yang J, Zhao X, Guo R, Zhang Y, Shen Y, Göke J, Liu L*, Lu X*. Zscan4c activates endogenous retrovirus MERVL and cleavage embryo genes. Nucleic Acids Res 47(16):8485-8501 (2019).
Sheng XY#, Tian CL#, Liu LL, Wang LL, Ye XY, Li J, Liu L*. Characterization of oogonia stem cells in mice by Fragilis. Protein Cell 10(11):825-831 (2019).
Guo RP, Ye XY, Yang J, Zhou ZC, Tian CL, Wang H, Wang HY, Fu HF, Liu C, Zeng M, Yang J & Liu L. Feeders facilitate telomere maintenance and chromosomal stability of embryonic stem cells. Nature Communications 9(1):2620 (2018).
Zhou Z, Wang L, Ge F, Gong P, Wang H, Wang F, Chen L, Liu L*. Pold3 is required for genomic stability and telomere integrity in embryonic stem cells and meiosis. Nucleic Acids Res 46(7):3468-3486 (2018).
Wang H, Zhang K, Liu YF, Fu YD, Gao S, Gong P, … Liu L. Telomere heterogeneity linked to metabolism and pluripotency state revealed by simultaneous analysis of telomere length and RNA-seq in the same human embryonic stem cell. BMC Biol 15(1):114 (2017).
Liu L. Linking telomere regulation to stem cell pluripotency. Trends in Genetics 33:16-33 (2017).
Yang J, Guo R, Wang H, Ye X, Zhou Z, Dan J, Wang H, Gong P, Deng W, Yin Y, Mao S, Wang L, Ding J, Li J, Keefe DL, Dawlaty MM, Wang J, Xu G, Liu L. Tet enzymes regulate telomere maintenance and chromosomal stability of mouse ESCs. Cell Reports 15:1809-1821 (2016).
Zhang H, Panula S, Petropoulos S, Edsgard D, Busayavalasa K, Liu L, Li X, Risal S, Shen Y, Shao J, Liu M, Li S, Zhang D, Zhang X, Gerner RR, Sheikhi M, Damdimopoulou P, Sandberg R, Douagi I, Gustafsson JA, Liu L, Lanner F, Hovatta O, Liu K. Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem cells. Nature Medicine 21:1116-1118 (2015).
Chen H, Guo R, Zhang Q, Guo H, Yang M, Wu Z, Gao S, Liu L, Chen L. Erk signaling is indispensable for genomic stability and self-renewal of mouse embryonic stem cells. Proc Natl Acad Sci USA. 112: E5936–E5943 (2015).
Sung LY, Chang WF, Zhang Q, Liu CC, Liou JY, Chang CC, Ou-Yang H, Guo RP, Fu HF, TK Cheng, Ding ST, Chen CM, Okuka M, Keefe DL, Chen YE, Liu L, Xu J. Telomere elongation and naive pluripotent stem cells achieved from telomerase haplo-insufficient cells by somatic cell nuclear transfer. Cell Reports 9:1603–1609 (2014).
Dan J, Y Liu, N Liu, M Chiourea, M Okuka, T Wu, X Ye,C Mou, LWang, LL Wang, Y Yin, J Yuan, B Zuo, F Wang, Z Li, XPan, ZYin, L Chen, DL Keefe,S Gagos, A Xiao, Liu L. Rif1 maintains telomere length homeostasis of ES cells by mediating heterochromatin silencing. Developmental Cell 29: 7–19 (2014).
Yuan J, Zhang D, Wang L, Liu M, Mao J, Yin Y, Ye X, Liu N, Han J, Gao Y, Cheng T, Keefe DL, Liu L. No evidence for neo-oogenesis may link to ovarian senescence in adult monkey. Stem Cells 31:2538-2550 (2013).
Wang F, Pan X, Kalmbach K, Seth-Smith ML, Ye X, Antumes DM, Yin Y, Liu L, Keefe DL, Weissman SM. Robust measurement of telomere length in single cells. Proc Natl Acad Sci USA. 110:E1906-1912 (2013).
Jiang J, Lv W, Ye X, Wang L, Zhang M, Yang H, Okuka M, Zhou C, Zhang X, Liu L, Li J. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. Cell Research 23:92-106 (2013).
Liu M, Yin Y, Ye X, Zeng M, Zhao Q, Keefe DL, Liu L. Resveratrol protects against age-associated infertility in mice. Human Reproduction 28:707-717 (2013).
Wang F, Yin Y, Ye X, Liu K, Zhu H, Wang L, Chiourea M, Okuka M, Ji G, Dan J, Zuo B, Li M, Zhang Q, Liu N, Chen L, Pan X, Gagos S, Keefe DL, Liu L. Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells. Cell Research 22:757-768 (2012).
Huang J, Wang F, Okuka M, Liu N, Ji G, Ye X, Zuo B, Li M, Liang P, Ge WW, Tsibris JC, Keefe DL, Liu L. Association of telomere length with authentic pluripotency of ES/iPS cells. Cell Research 21:779-792 (2011).
Agarwal S, Loh YH, McLoughlin EM, Huang J, Park IH, Miller JD, Huo H, Okuka M, Dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464:292-296 (2010).
Huang J, Okuka M, Wang F, Zuo B, Liang P, Kalmbach K, Liu L, Keefe DL. Generation of pluripotent stem cells from eggs of aging mice. Aging Cell 9:113-125 (2010).
Li C, Chen Z, Liu Z, Huang J, Zhang W, Zhou L, Keefe DL, Liu L. Correlation of expression and methylation of imprinted genes with pluripotency of parthenogenetic embryonic stem cells. Human Molecular Genetics 18:2177-2187 (2009).
Chen Z, Liu Z, Huang J, Amano T, Li C, Cao S, Wu C, Liu B, Zhou L, Carter MG, Keefe DL, Yang X, Liu L. Birth of Parthenote mice directly from parthenogenetic embryonic stem cells. Stem Cells 27:2136-2145 (2009).
Huang J, Deng K, Wu H, Liu Z, Chen Z, Cao S, Zhou L, Ye X, Keefe DL, Liu L. Efficient production of mice from embryonic stem cells injected into four- or eight-cell embryos by piezo micromanipulation. Stem Cells 26:1883-1890 (2008).
Liu L, S. M. Bailey, M. Okuka, P. Mu?oz, C. Li, L. Zhou, C. Wu, E. Czerwiec, L. Sandler, A. Seyfang, M. A. Blasco and Keefe. D. L. Telomere lengthening early in development. Nature Cell Biology 9: 1436-1441 (2007).
Dai, Y., L. Wang, H. Wang, Y. Liu, Q. Lyu, N. Li, D.L. Keefe, D.F. Albertini and L. Liu. Abnormalities in centrosome remodeling following somatic cell nuclear transfer (SCNT) in bovine oocytes. Reproduction 131:1051-1061 (2006).
Liu, L., Franco, S., Spyropoulos, B., Moens, P.B., Blasco, M.A., and Keefe, D.L. Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci U S A 101: 6496-6501 (2004).
Liu, L. and D.L. Keefe. Ageing-associated aberration in meiosis of oocytes from Senescence-Accelerated Mouse (SAM). Human Reproduction 17: 2678-2685 (2002).
Liu, L., M.A. Blasco and D.L. Keefe. Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO Reports 3:230-234 (2002).
Liu, L., J.R. Trimarchi, P. Smith and D.L. Keefe. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell 1:40-46 (2002).
Dinnyés, A., Dai, Y., Barber, M., Liu, L., Xu, J., Zhou, P., and Yang, X. Development of cloned embryos from adult rabbit fibroblasts: effect of activation treatment and donor cell preparation. Biology of Reproduction 64: 257-263 (2001).
Liu, L. Cloning efficiency and differentiation. Nature Biotechnology 19:406 (2001).
Liu, L., Oldenbourg, R., Trimarchi, J.R., and Keefe, D.L. A reliable, noninvasive technique for spindle imaging and enucleation of mammalian oocytes. Nature Biotechnology 18: 223 – 225 (2000).
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