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

doi:10.1016/j.celrep.2023.112645

Culture conditions of mouse ESCs impact the tumor appearance in vivo

Cell Rep. 2023 Jun 27;42(6):112645. doi: 10.1016/j.celrep.2023.112645. Epub 2023 Jun 13.

Authors

Chenglei Tian¹, Jing Wang², Xiaoying Ye¹, Jiyu Chen¹, Rongyan Zheng³, Hanwen Yu³, Jie Li¹, Guoxing Yin¹, Linlin Liu¹, Nannan Zhao⁴, Guofeng Feng¹, Zhengmao Zhu¹, Jichang Wang⁵, Guoping Fan⁶, Lin Liu⁷

Affiliations

¹ 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.
² 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.
³ Key Laboratory for Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
⁴ Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin 300071, China.
⁵ Key Laboratory for Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: wangjch53@mail.sysu.edu.cn.
⁶ 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. Electronic address: guopingfan@gmail.com.
⁷ 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. Electronic address: liulin@nankai.edu.cn.

PMID: 37314926
DOI: 10.1016/j.celrep.2023.112645

Abstract

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.

Keywords: CP: Stem cell research; chromatin accessibility; methylation; mice; pluripotent stem cells; teratoma; tetraploid embryo complementation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Embryonic Stem Cells
Mice
Mouse Embryonic Stem Cells / pathology
Pluripotent Stem Cells*
Teratoma* / pathology