干细胞毒理学课题组利用干细胞，重点探索传统、新型环境污染物的健康效应问题，并构建胚胎毒性、发育毒性、生殖毒性和细胞功能测试的实验模型，有望阐释目前环境污染物的健康危害及致毒机制，提出有效的预防与防治措施，为环境污染物的健康效应研究作出贡献。

　　本课题组组长Francesco Faiola研究员在干细胞生物学，分子生物学和生物化学领域具备深厚的研究背景，于2014年就职于生态环境研究中心，在中科院生态环境中心领导建立了国际上第一个干细胞毒理学实验室。现为环境化学与生态毒理学国家重点实验室

研究方向：1.利用鼠源和人源多种干细胞，对环境污染物的急性毒性、胚胎毒性、发育毒性、器官毒性、生殖毒性和细胞功能性毒性进行评价。 
2.解析环境污染物对干细胞以及由干细胞衍生的祖细胞和终端分化细胞系的毒性作用机制

联系方式：Email：faiola@rcees.ac.cn; 电话：010-62849096；传真：010-62849096

承担项目：
1. 中国科学院战略性先导科技专项（B类）（XDB14040300）典型污染物诱导干细胞癌变的机理，2014.06-2019.05 
2. 国家自然科学基金面上项目（21577166），利用多能干细胞研究环境污染物的健康效应及风险评估，2016.01-2019.12 
3. 国家自然科学基金面上项目（21577167），新型持久性环境污染物对间充质干细胞自我更新和分化能力的影响机制，2016.01-2019.12

　　干细胞毒理学研究 

　　费凡*，殷诺雅，姚醒蕾，江桂斌 

　　研究组结合环境毒理学和干细胞生物学，在国际上首次明确提出研究环境污染物“干细胞毒理学”，相应观点作为Viewpoint发表于Environ. Sci & Technol。近年来，新型持久性环境污染物数量逐年递增，而相应的毒理学效应尚不明确，越来越多的研究者意识到，建立一个切实有效的人类健康相关的综合性毒理学分析方法迫在眉睫。但传统毒理学研究多依赖于动物模型，尽管近年来该方法已经取得长足进展，却依然面临着成本过高、费时费力以及备受动物伦理争议等诸多问题。相对于传统体外毒理学研究模型的局限性，干细胞技术在毒理学研究中的应用为该领域带来了全新的思路和优势：1）干细胞在污染物的急性毒性测试中往往比普通体细胞更加敏感；2）干细胞在污染物作用下分化的异常表型可以作为胚胎发育毒性的最佳判断标准，可以用来模拟人体胚胎发育的早期阶段；3）干细胞可分化为各种终末端的体细胞，用于不同类型的功能性分析；4）污染物对人类生殖能力的影响越来越受到关注，而多能性干细胞是体外研究污染物对生殖系统毒性影响的最佳模型。

干细胞毒理学实验方法示意图

组长  Francesco Faiola (费凡) 研究员

工作人员

重要成果：

1. Shuyu Liu, Nuoya Yin, and Francesco Faiola*. PFOA and PFOS Disrupt the Generation of Human Pancreatic Progenitor Cells. Environmental Science & Technology Letters. 2018 5(5), 237-242

2. Nuoya Yin#, Renjun Yang#, Shaojun Liang, Shengxian Liang, Bowen Hu, Ting Ruan, Francesco Faiola*. Evaluation of the early developmental neural toxicity of F-53B, as compared to PFOS, with an in vitro, mouse stem cell differentiation model. Chemosphere. 2018, 204, 109-118. 
#These authors contributed equally.

3. Nuoya Yin#, Shaojun Liang#, Shengxian Liang, Renjun Yang, Bowen Hu, Zhanfen, Qin, Aifeng Liu, Francesco Faiola*. TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways. Environmental Science & Technology. 2018 52 (9), 5459-5468. 
#These authors contributed equally.

4. Nuoya Yin#, Shengxian Liang#, Shaojun Liang, Bowen Hu, Renjun Yang, Qunfang Zhou, Guibi Jiang, Francesco Faiola*. DEP and DBP induce cytotoxicity in mouse embryonic stem cells and abnormally enhance neural ectoderm development. Environmental Pollution. 2018, 236:21. 
#These authors contributed equally.

5. Shuyu Liu, Nuoya Yin, Francesco Faiola*. Prospects and Frontiers of Stem Cell Toxicology. Stem Cells & Development. 2017, 26(21):1528-1539.

6. Francesco Faiola#*, Nuoya Yin#, Miguel Fidalgo, Xin Huang, Arven Saunders, Junjun Ding, Diana Guallar, Baoyen Dang, and Jianlong Wang*. NAC1 Regulates Somatic Cell Reprogramming by Controlling Zeb1 and E-cadherin Expression. Stem Cell Reports. 2017, 9(3):913-926. 
#These authors contributed equally.

7. Francesco Faiola*, Nuoya Yin, Xinglei Yao, and Guibin Jiang. The rise of stem cell toxicology. Environmental Science & Technology. 2015, 49(10):5847-5848.

8. Nuoya Yin, Xinglei Yao, Qunfang Zhou, Francesco Faiola*, Guibin Jiang. Vitamin E attenuates silver nanoparticle-induced effects on body weight and neurotoxicity in rats. Biochemical and Biophysical Research Communications. 2015, 458(2):405-410.

9. Nuoya Yin, Xinglei Yao, Zhanfen Qin, Yuan-Liang Wang, Francesco Faiola*. Assessment of Bisphenol A (BPA) neurotoxicity in vitro with mouse embryonic stem cells. Journal of Environmental Sciences. 2015, 36:181-187.

10. Junjun Ding, Xin Huang, Ningyi Shao, Hongwei Zhou, Dung-Fang Lee, Francesco Faiola, Miguel Fidalgo, Diana Guallar, Arven Saunders, Pavel V. Shliaha, Hailong Wang, Avinash Waghray, Dmitri Papatsenko, Carlos S nchez-Priego, Dan Li, Ye Yuan, Ihor R. Lemischka, Li Shen, Kevin Kelley, Haiteng Deng, Xiaohua Shen, Jianlong Wang*. Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming. Cell Stem Cell. 2015, 16(6):653-668.

11. Yael Costa,# Junjun Ding,# Thorold W#. Theunissen,# Francesco Faiola,# Timothy A. Hore, Pavel V. Shliaha, Miguel Fidalgo, Arven Saunders, Moyra Lawrence, Sabine Dietmann, Satyabrata Das, Dana N. Levasseur, Zhe Li, Mingjiang Xu, Wolf Reik, Jos C.R. Silva, and Jianlong Wang*. NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature. 2013, 495(7441):370-374. 
#These authors contributed equally.

12. Julian A. Gingold, Miguel Fidalgo, Diana Guallar, Zerlina Lau, Zhen Sun, Hongwei Zhou, Francesco Faiola, Xin Huang, Dung-Fang Lee, Avinash Waghray, Christoph Schaniel, Dan P. Felsenfeld, Ihor R. Lemischka, Jianlong Wang*. A genome-wide RNAi screen identifies opposing functions of Snai1 and Snai2 on the Nanog dependency in reprogramming. Molecular Cell. 2014, 56(1):140-152.

13. Miguel Fidalgo, Francesco Faiola, Carlos-Filipe Pereira, Junjun Ding, Arven Saunders, Julian Gingold, Christoph Schaniel, Ihor R. Lemischka, Jos C. R. Silva, and Jianlong Wang*. Zfp281 mediates Nanog autorepression through recruitment of the NuRD complex and inhibits somatic cell reprogramming. Proceedings of the National Academy of Sciences of the United States of America. 2012, 109(40):16202-16207.

14. Junjun Ding, Huilei Xu,# Francesco Faiola,# Avi Ma'ayan, Jianlong Wang*. Oct4 links multiple epigenetic pathways to the pluripotency network. Cell Research. 2012, 22(1):155-167. 
#These authors contributed equally.

15. Yuan-Liang Wang, Francesco Faiola, Muyu Xu, Songqin Pan, and Ernest Martinez*. Human ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein. The Journal of Biological Chemistry. 2008, 283(49):33808-33815. (Selected for Faculty of 1000 Biology).

16. Francesco Faiola,# Xiaohui Liu,# Szuying Lo, Songqin Pan, Kangling Zhang, Elena Lymar, Anthony Farina, and Ernest Martinez. Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. Molecular and Cellular Biology. 2005, 25(23):10220-10234. 
#These authors contributed equally.