但佳猛 (Jiameng Dan)

2024年11月—至今，昆明理工大学灵长类转化医学研究院，教授，博士生导师

2021年05月-2024年11月，昆明理工大学灵长类转化医学研究院，校聘教授

2017年12月-2021年04月，美国加州索尔克生物研究所 (Salk Institute)，助理研究员

2014年11月-2017年12月，美国德克萨斯大学MD安德森癌症中心 (MD Anderson Cancer Center)，博士后

2007年09月-2014年06月，南开大学生命科学学院，细胞生物学专业，干细胞与发育生物学研究方向获理学博士学位 (硕博连读)

1. 胚胎干细胞多能性与全能性的维持与转换调控机制

哺乳动物早期胚胎材料有限，特别是灵长类胚胎更加不易获得，进而严重制约着对早期胚胎发育的研究。全能性在小鼠里面局限于受精卵和2细胞期胚胎，在人里面局限于受精卵和4-8胚胎期之前的卵裂球，具备同时向胎儿和胎盘组织分化的潜能。合子基因组激活（Zygotic genome activation, ZGA）在小鼠里面发生在2细胞胚胎期，在人里面发生在8细胞胚胎期。最近在小鼠和人的胚胎干细胞（naïve embryonic stem cells, naïve ESCs）群体中分别发现占比1%左右的二细胞胚胎样细胞（2C-like cells, 2CLCs）和八细胞胚胎样细胞（8C-like cells, 8CLCs）。2CLCs与8CLCs和ZGA发生时期早期胚胎共享诸多分子及表观遗传特征，2CLCs更进一步证实为全能样细胞，已成为研究早期胚胎发育的良好体外模型。我们将利用全能样体外细胞模型和体内胚胎深入探讨多能性与全能性维持及相互转换的机制、哺乳动物（包括人和猴）早期胚胎全能性获得、合子基因组激活和快速退出的核心调控因子的鉴定和作用机制、表观遗传维持与重建调控机制等重要科学问题。

2. 早期胚胎发育表观遗传调控机制

哺乳动物早期胚胎发育从受精卵到囊胚期经历了剧烈的表观遗传重构过程，包括全基因组DNA的去甲基化，从而确保胚胎发育的正常进行。我们将深入探讨早期胚胎发育过程中全基因组DNA去甲基化的生物学意义及调控机制，并探讨相关调控及维持机制在灵长类动物早期胚胎发育进程中的保守性，为人类生殖健康提供科学依据及临床解决方案。

1. Regulation and maintenance of pluripotency and totipotency

The scarcity of mammalian early embryos, especially embryos from primates, greatly restricts our understanding of early embryogenesis. Only zygotes and 2C embryos in mice, zygotes and embryos before 4-8 stage in human, are recognized to be totipotent. Zygotic genome activation (ZGA) occurs at 2C stage in mice and 8C stage in human, respectively. Recently, it has been shown that a small population (1%) called 2C-like cells (2CLCs) in mouse naïve ESC and 8C-like cells (8CLCs) in human naïve ESCs culture share many molecular and epigenetic features with 2C embryos in mice and 8C embryos in human, respectively. Importantly, 2CLCs are demonstrated to be totipotent-like cells, which can give rise to both embryonic and extraembryonic tissues. Thus, both 2CLCs and 8CLCs are ideal in vitro models for investigating embryogenesis. We will apply these in vitro cell models to investigate the mechanisms underlying the maintenance and transition between pluripotency and totipotency, early embryo totipotency acquisition, ZGA entry and exit, epigenetic maintenance and reprogramming.

2. Epigenetic regulation in early embryogenesis

It is well known that the preimplantation embryo development processes are accompanied with dramatic epigenetic reprogramming, including global DNA demethylation, which ensures proper embryogenesis. We aim to decipher the biological significance and mechanisms regulating global DNA demethylation processes in early embryo development, and investigate whether the mechanisms are conserved in primates. The study will provide scientific clues and potential strategies to improve reproductive health in mammals, especially in primates.

1. 国家自然科学基金面上项目，二细胞胚胎样干细胞获得发育全能性的机制研究，32270845, 2023-01至2026-12，54万元，主持。

2. 云南省“兴滇英才支持计划”青年人才项目支持计划，哺乳动物早期发育胚胎中介导DNMT1细胞质定位 的截留因子鉴定及其作用机制研究，2022-12至2027-12，KKRD202273103，90万元，主持。

3. 云南省科技厅/昆明理工大学“双一流”创建联合专项重点项目，哺乳动物原始生殖细胞发育过程中DNA去甲基化重编程的生物学意义研究，2022-10至2025-09，202201BE070001-006，100万元，主持。

4. 云南省基础研究专项面上项目，哺乳动物早期胚胎发育DNA去甲基化重编程的生物学意义研究，2023-06至2026-05，10万元，主持。

5. 昆明理工大学灵长类转化医学研究院高层次人才启动经费，主持。

6. 美国德州大学MD安德森癌症中心校内短期项目，2016-05至2017-05，6万美元（约40万元人民币），主持。

2021年回国以后

1.Guo D#, Du Z#, Liu Y#, Lin M, Lu Y, Hardikar S, Xue Y, Zhang J, Chen T, Dan J*. The ZBTB24-CDCA7-HELLS axis suppresses the totipotent 2C-like reprogramming by maintaining Dux methylation and repression. Nucleic Acids Research. 2025 Apr 10;53(7):gkaf302.

2.Lin M, Du Z, Guo D, Zhang Y, Dan J*. Dux cluster duplication ensures full activation of totipotent genes. Proc Natl Acad Sci USA. 2025 Mar 11;122(10):e2421594122.

3.Yang J#, Dan J#, Zhao N, Liu L, Wang H, Liu Q, Wang L, Li J, Wu Y, Chen F, Fu W, Liu F, Lin M, Zhang W, Chen F, Liu X, Lu X, Chen Q, Wu X, Niu Y*, Yang N*, Zhu Y*, Long J*, Liu L*. Zscan4 mediates ubiquitination and degradation of the corepressor complex to promote chromatin accessibility in 2C-like cells. Proc Natl Acad Sci USA. 2024 Dec 24;121(52):e2407490121.

4.Du Z#, Lin M#, Li Q#, Guo D, Xue Y, Liu W, Shi H, Chen T, Dan J*. The totipotent 2C-like state safeguards genomic stability of mouse embryonic stem cells. Journal of Cellular Physiology. 2024 Sep;239(9):331337.

5.Hardikar S#, Ren R#, Ying Z#, Zhou J#, Horton JR, Bramble MD, Liu B, Lu Y, Liu B, Coletta LD, Shen J, Dan J, Zhang X, Cheng X*, Chen T*. The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA. Science Advances. 2024 Aug 23;10(34):eadr0036.

6.Dan J*, Du Z, Zhang J, Chen T*. The interplay between H3K36 methylation and DNA methylation in cancer. Cancer Biol Med. 2023 Aug 18;20(8):545-52.

7.Dan J* and Chen T*. Writers, erasers, and readers of DNA and histone methylation marks (Book chapter). Epigenetic Cancer Therapy. 2023;39-63

8.Dan J* and Chen T*. Genetic Studies on Mammalian DNA Methyltransferases (2nd Edition). Adv Exp Med Biol. 2022; 1389:111-136.

9.Dan J*, Zhou Z, Wang F, Wang H, Guo R, Keefe DL, Liu L*. Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells. Cells. 2022 Jan 28;11(3):456.

2021年回国前

1.Dan J#, Memczak S#, Belmonte JCI*. Expanding the Toolbox and Targets for Gene Editing. Trends in Molecular Medicine, 2021 Mar;27(3):203-206.

2.Dan J, Rousseau P, Hardikar S, Veland N, Wong J, Autexier C, Chen T*. Zscan4 Inhibits Maintenance DNA Methylation to Regulate Telomere Elongation in Mouse Embryonic Stem Cells. Cell Reports. 2017 Aug 22;20(8):1936-1949.

3.Dan J#, Liu Y#, Liu N#, Chiourea M, Okuka M, Wu T, Ye X, Mou C, Wang L, Wang L, Yin Y, Yuan J, Zuo B, Wang F, Li Z, Pan X, Yin Z, Chen L, Keefe DL, Gagos S, Xiao A*, Liu L*. Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing. Developmental Cell. 2014 Apr 14;29(1):7-19.

4.Dan J and Chen T*. Genetic Studies on Mammalian DNA Methyltransferases. Adv Exp Med Biol. 2016; 945:123-150.

5.Dan J, Yang J, Liu Y, Xiao A, Liu L*. Roles for Histone Acetylation in Regulation of Telomere Elongation and Two-Cell State in Mouse ES Cells. Journal of Cellular Physiology. 2015 Oct; 230(10):2337-44.

6.Dan J, Li M, Yang J, Li J, Okuka M, Ye X, Liu L*. Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells. Scientific Reports. 2013 Dec 13; 3:3492.

7.Liu H#, Li R#, Liao H#, Min Z, Wang C, Yu Y, Shi L, Dan J, Nunez E, Martinez L, Wu J, Belmonte JCI*. Novel chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells. Nature Communications. 2021 Jun 7;12(1):3330.

8.Veland N, Zhong Y, Gayatri S, Dan J, Strahl B, Rothbart S, Bedford M, Chen T*. The Arginine Methyltransferase PRMT6 Regulates DNA Methylation and Contributes to Global DNA Hypomethylation in Cancer. Cell Reports. 2017 Dec 19;21(12):3390-3397.

9.Kim J#, Zhao H#, Dan J, Kim S, Hardikar S, Hollowell D, Lin K, Lu Y, Takata Y, Shen J, Chen T*. Maternal Setdb1 is required for meiotic progression and preimplantation development in mouse. PLoS Genetics. 2016 Apr 12;12(4):e1005970.

10.Yang J, Guo R, Wang H, Zhou Z, Ye X, Dan J, Wang H, Gong T, Deng W, Yin Y, Mao S, Wang L, Ding J, Li J, Dawlaty M, Wang J, Xu G, Liu L*. Tet Enzymes Regulates Telomere Maintenance and Chromosomal Stability of Mouse ESCs. Cell Reports. 2016 May 24;15(8):1809-21.

11.Zhang Q, Dan J, Wang H, Guo R, Mao J, Fu H, Wei X, Liu L*. Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells. Scientific Reports. 2016 Jan 27; 6:19852.

12.Wang L, Ye X, Zhao Q, Zhou Z, Dan J, Zhu Y, Chen Q, Liu L*. Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but required for differentiation of ES cells. Stem Cell and Development. 2014 Oct 15;23(20):2422-34.

13.Hao J, Li W, Dan J, Ye X, Wang F, Zeng X, Wang L, Wang H, Cheng Y, Liu L*, Shui W*. Reprogramming- and pluripotency-associated membrane proteins in mouse stem cells revealed by label-free quantitative proteomics. Journal of Proteomics. 2013 Jun 28; 86:70-84.

14.Zuo B#, Yang J#, Wang F, Wang L, Yin Y, Dan J, Liu N, Liu L*. Influences of lamin A levels on induction of pluripotent stem cells. Open Biology. 2012 Nov 15;1(11):1118-27.

15.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. 2012 Apr;22(4):757-68.

1. 欢迎优秀的本科生和硕士生报考本实验室的硕士和博士研究生。

2. 实验室招聘博士后、助理研究员或讲师

要求具有分子、细胞、或发育生物学等相关学科背景，并（将）取得博士学位；有胚胎干细胞、早期胚胎发育研究或生物信息学分析经验者优先； 2）以第一作者发表过SCI论文1篇以上，能独立开展科研工作，并协助指导研究生；3）具有较好的思辨能力及较强的自我激励动力，较好的交流能力和团队合作精神；4）具备较好的英文听、说、读、写能力。

有意者请将简历和支撑材料发送至danjm@lpbr.cn