Culture conditions of mouse ESCs impact the tumor appearance in vivo
Chenglei Tian,
Jing Wang,
Xiaoying Ye,
Jiyu Chen,
Rongyan Zheng,
Hanwen Yu,
Jie Li,
Guoxing Yin,
Linlin Liu,
Nannan Zhao,
Guofeng Feng,
Zhengmao Zhu,
Jichang Wang,
Guoping Fan,
Lin Liu
Affiliations
Chenglei Tian
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Jing Wang
Department of Human Genetics and Broad Stem Cell Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Xiaoying Ye
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Jiyu Chen
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Rongyan Zheng
Key Laboratory for Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Hanwen Yu
Key Laboratory for Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Jie Li
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Guoxing Yin
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Linlin Liu
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Nannan Zhao
Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Guofeng Feng
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Zhengmao Zhu
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China
Jichang Wang
Key Laboratory for Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Guoping Fan
Department of Human Genetics and Broad Stem Cell Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China; Corresponding author
Lin Liu
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China; Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China; Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin 300071, China; Corresponding author
Summary: Various culture conditions by small molecules have been explored to extend pluripotency of stem cells, but their impacts on cell fate in vivo remain elusive. We systematically compared the effects of various culture conditions on the pluripotency and cell fate in vivo of mouse embryonic stem cells (ESCs) by tetraploid embryo complementation assay. Conventional ESC cultures in serum/LIF-based condition produced complete ESC mice and also the survival to adulthood at the highest rates of all other chemical-based cultures. Moreover, long-term examination of the survived ESC mice demonstrated that conventional ESC cultures did not lead to visible abnormality for up to 1.5–2 years, whereas the prolonged chemical-based cultures developed retroperitoneal atypical teratomas or leiomyomas. The chemical-based cultures exhibited transcriptomes and epigenomes that typically differed from those of conventional ESC cultures. Our results warrant further refinement of culture conditions in promoting the pluripotency and safety of ESCs in future applications.
