1.从小鼠8细胞期胚胎和单个卵裂球分离，建株一种新型的胚胎干细胞，扩增潜能多能干细胞(Expanded potential stem cell, EPSC)。这些干细胞具有向胚胎和胚外组织分化的潜能，为研究小鼠早期胚胎发育提供了新的细胞来源和工具。2.首先建立了体外将naïve 胚胎干细胞（embryonic stem cells, ESCs）转化为Primed 上胚层干细胞（epiblast stem cells, EpiSCs）的培养系统，随后，阐明了Jak/STAT3和维甲酸信号通路在EpiSCs和体细胞重编程中的重要作用和机制。3. 运用CRISPRa对小鼠全基因组进行筛选能重编程EpiSCs的因子，发现了一些新的因子，并证实它们具有重编程功能。重点研究了Sall1, Nanog这两个基因，发现两者在EpiSCs和成纤维细胞重编程中有协同作用，进一步发现并证实了它们下游各自的靶基因。 4. 建立了高效的心脏起搏细胞分化系统，体内外研究证实其生物起搏功能。5. 阐明了转录因子HAND在人多能干细胞分化为心肌细胞中的功能和机制。6. 制备了新型氧化铈纳米酶并验证其对干细胞和心肌细胞氧化应激的保护作用。
1. We established a new type of embryonic stem cell-Expanded potential stem cell (EPSCs) from mouse 8C embryo and single blastomere. The EPSCs can contribute to both embryonic and extraembryonic tissues, which provide a new tool and cell resource for the study of mouse early embryo development. 2. We first developed an in vitro culture system to convert naïve embryonic stem cells (ESCs) into primed epiblast stem cells (EpiSCs), then clarified roles of Jak/STAT3 and Retinoic Acid signaling pathways in reprogramming primed EpiSCs and somatic cells into naïve iPSCs and the related molecular mechanism. 3. By mouse whole genome CRISPRa screen, we identified and validated some new reprogramming factors. Particularly, we discovered that SALL1 and NANOG not only facilitate EpiSCs and fibroblasts reprogramming, but also have synergistic effects. Furthermore, we revealed the downstream targets of SALL1 and NANOG in reprogramming. 4. We established highly efficient cardiac pacemaker cell (PC) differentiation system. Both in vivo and in vitro evaluation demonstrated the pacemaker characteristics of the PCs. 5. By applying cardiomyocyte (CM) differentiation system, we revealed the essential function of transcription factors-HAND1,2 in early heart development and one of the key targets-TBX5. 6. We generated a new type of nanoparticle-CeONZs and confirmed their effects on protecting pluripotent stem cells and cardiomyocytes from oxidative stress.
承担的项目：
国家自然科学基金基础科学中心：重大心脏病的起源和干预，骨干
国家自然科学基金面上项目：Sall1调控多能干细胞naïve和primed状态转换的机制研究，负责人
国家自然科学基金重点项目：蛋白激酶介导的心肌细胞增殖在心肌损伤修复中的作用及机制研究，骨干
科技部“一带一路”创新人才交流外围专家项目：纳米生物材料在干细胞治疗心脏疾病中的安全、有效性研究 主持
中国医学科学院心律的起源与调控创新单元，骨干
上海市前沿科学研究基地：上海市催化医学前沿科学研究基地 骨干
发表的代表性文章：
Chengwen Hang, Mohamed S Moawad, Zheyi Lin, Huixin Guo, Mingshuai Zhang, Renhong Lu, Junnyang Liu, Dan Shi, Duanyang Xie, Yi Liu, Dandan Liang, Yi-Hann Chen, Jian Yang. Biosafe cerium oxide nanoenzymes protect human pluripotent stem cells and cardiomyocytes from oxidative stress. Journal of Nanobiotechnology, Co-corresponding author, 2024. 22(1): 132. Doi: 10.1186/s12951-024-02383-x.
Huixing Guo, Chengwen Hang, Bowen Lin, Zheyi Lin, Hui Xiong, Mingshuai Zhang, Rehong Lu, Junyang Liu, Dan Shi, Duanyang Xie, Yi Liu, Dandan Liang, Jian Yang, Yi-Han Chen. HAND factors regulate cardiac lineage commitment and differentiation from human pluripotent stem cells. Stem Cell Research and Therapy, Co-corresponding author, 2024. 15(1): 31. Doi: 10.1186/s13287-024-03649-9.
Le Ni, Bowen Lin, Lingjie Hu, Ruoyu Zhang, Fengmei Fu, Meiting Shen, Jian Yang, Dan Shi. Pyruvate kinase M2 protects heart from pressure overload-induced heart failure by phosphorylating RAC1. Journal of the American Heart Association, Co-corresponding author, 2022. Jun 7, 11(11): e024854. Doi: 10.1161/JAHA.121.024854
Jingjing Liu, Xianting Ke, Luxin Wang, Yangyang Zhang, and Jian Yang. Deficiency of cold-inducible RNA-binding protein exacerbated monocrotaline-induced pulmonary artery hypertension through Caveolin1 and CAVIN1. Journal of Cellular and Molecular Medicine, Co-corresponding author, online March 23, 2021. 25(10): 4732-4743 Doi: 10.1111/jcmm.16437.
Jian Yang, Haifeng Fu, Cheryl Tam and Pentao Liu. Expanded potential: the key to synthetic embryo? Co-corresponding author, Current Opinion in Genetics and Development, 2020, 64: 72-77.
Nicholas Bredenkamp, Jian Yang, James Clarke, Giuliano Giuseppe Stirparo, Ferdinand von Meyenn, Sabine Dietmann, Duncan Baker, Rosalind Drummond, Yongming Ren, Chuman Wu, Maria Rostovskaya, Sarah Eminli-Meissner, Austin Smith, and Ge Guo. Wnt inhibition facilitates RNA-mediated reprogramming of human somatic cells to naïve pluripotency. Co-first author, Stem Cell Reports, 2019, 13(6): 1083-1098
Jian Yang, Sandeep S. Rajan, Mathias J Friedrich, Guocheng Lan, Xiangang Zou, Hannes Ponsting, Dimitrios A Garyfallos, Pentao Liu, Allan Bradley, and Emmanouil Metzakopian. Genome-scale CRISPRa screen identifies novel factors for cellular reprogramming. Co-first author, Stem Cell Reports, 2019, 12(4):754-771
Jian Yang, David Ryan, Guocheng Lan, Xiangang Zou and Pentao Liu*. Establishment in vitro of Expanded Potential Stem Cells from mouse preimplantation embryos and embryonic stem cells. Co-corresponding author, Nature Protocols, 2019, 14, 350-378
Jian Yang, David J. Ryan, Wei Wang, Jason Cheuk-Ho Tsang, Guocheng Lan, Hideki Masaki, Xuefei Gao, Liliana Antunes, Yong Yu, Zhexin Zhu, Juexuan Wang, Aleksandra A. Kolodziejczyk, Lia S. Campos, Cui Wang, Fengtang Yang, Zhen Zhong, Beiyuan Fu, Melanie Eckersley-Maslin, Michael Woods, Yosuke Tanaka, Xi Chen, Adam C. Wilkinson, James Bussell, Jacqui White, Ramiro Ramirez-Solis, Wolf Reik, Berthold Göttgens, Sarah A. Teichmann, Patrick P. L. Tam, Hiromitsu Nakauchi, Xiangang Zou, Liming Lu and Pentao Liu. Establishment of murine expanded potential stem cells. Co-first author, Nature, 2017, 550, 393-397.
Jian Yang, Wei Wang, Jolene Ooi, Lia Campos, Liming Lu and Pentao Liu. Signaling through retinoic acid receptors is required for reprogramming of both MEFs and EpiSCs to iPSCs. Stem Cells, 2015, 33(5): 1390-1404.
Jian Yang, Anouk L. van Oosten, Thorold W. Theunissen, Ge Guo, Jose C.R. Silva and Austin Smith Stat3 Activation Is Limiting for Reprogramming to Ground State Pluripotency. Cell Stem Cell, 2010, 7(3): 319-328.
Jindun Zhang, Xuefei Gao, Jian Yang, Xiaoying Fan, Wei Wang, Yanfeng Liang, Lihong Fan, Hongmei Han, Xiaorong Xu, Fuchou Tang, Siqin Bao, Pentao Liu and Xihe Li. Xist intron 1 repression by TALE designer transcriptional factor improves somatic cell reprogramming in mice. Stem Cells, 2019, 37(5): 599-608.
Xuefei Gao, Jian Yang, Jason Tsang, Jolene Ooi, Donghai Wu and Pentao Liu. Reprogramming to Pluripotency Using Designer TALE Transcription Factors Targeting Enhancers. Stem Cell Reports, 2013, 1(2): 183-197.
Wei Wang, Jian Yang, Hui Liu, Dong Lu, Xiongfeng Chen , Zenon Zenonos, Lia S. Campos, Roland Rad, Ge Guo, Shujun Zhang, Allan Bradley, and Pentao Liu. Rapid and efficient reprogramming of somatic cells to induced pluripotent stem cells by retinoic acid receptor gamma and liver receptor homolog 1. Proc Natl Acad Sci U.S.A, 2011, 108(45): 18283-18288.
Ge Guo, Jian Yang, Jennifer Nichols, John Simon Hall, Isobel Eyres, William Mansfield and Austin Smith. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development, 2009, 136(7): 1063-1069.
Mia Buehr,Stephen Meek,Kate Blair,Jian Yang,Janice Ure,Jose Silva,Renee McLay,John Hall,Qi-Long Ying andAustin Smith. Capture of Authentic Embryonic Stem Cells from Rat Blastocysts. Cell, 2008, 135(7): 1287-1298.
