Single-cell sequencing reveals the potential oncogenic expression atlas of human iPSC-derived cardiomyocytes
Minglin Ou,
Min Zhao,
Chunhong Li,
Donge Tang,
Yong Xu,
Weier Dai,
Weiguo Sui,
Yue Zhang,
Zhen Xiang,
Chune Mo,
Hua Lin,
Yong Dai
Affiliations
Minglin Ou
Central Laboratory, Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University, Guilin 541000, China
Min Zhao
GeneCology Research Centre/Seaweed Research Group, School of Science and Engineering, University of the Sunshine Coast, Queensland 4556, Australia
Chunhong Li
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Donge Tang
Clinical Medical Research Center, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China
Yong Xu
Clinical Medical Research Center, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China
Weier Dai
College of Natural Science, University of Texas at Austin, Austin 78712, Texas, USA
Weiguo Sui
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Yue Zhang
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Zhen Xiang
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Chune Mo
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Hua Lin
Guangxi Key laboratory of Metabolic Diseases Research, Central Laboratory of Guilin No. 181 Hospital, Guilin 541002, China
Yong Dai
Clinical Medical Research Center, The Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen 518020, China
Human induced pluripotent stem cells (iPSCs) are important source for regenerative medicine. However, the links between pluripotency and oncogenic transformation raise safety issues. To understand the characteristics of iPSC-derived cells at single-cell resolution, we directly reprogrammed two human iPSC lines into cardiomyocytes and collected cells from four time points during cardiac differentiation for single-cell sequencing. We captured 32,365 cells and identified five molecularly distinct clusters that aligned well with our reconstructed differentiation trajectory. We discovered a set of dynamic expression events related to the upregulation of oncogenes and the decreasing expression of tumor suppressor genes during cardiac differentiation, which were similar to the gain-of-function and loss-of-function patterns during oncogenesis. In practice, we characterized the dynamic expression of the TP53 and Yamanaka factor genes (OCT4, SOX2, KLF4 and MYC), which were widely used for human iPSCs lines generation; and revealed the co-occurrence of MYC overexpression and TP53 silencing in some of human iPSC-derived TNNT2+ cardiomyocytes. In summary, our oncogenic expression atlas is valuable for human iPSCs application and the single-cell resolution highlights the clues potentially associated with the carcinogenic risk of human iPSC-derived cells.