1.The genomic stability of induced pluripotent stem cells.
Zhao CHEN ; Tongbiao ZHAO ; Yang XU
Protein & Cell 2012;3(4):271-277
With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of human patients with defined factors, hold promise for regenerative medicine because they can provide a renewable source of autologous cells for cell therapy without the concern for immune rejection. In addition, iPSCs provide a unique opportunity to model human diseases with complex genetic traits, and a panel of human diseases have been successfully modeled in vitro by patient-specific iPSCs. Despite these progresses, recent studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to the immunogenicity of some cells differentiated from iPSCs. The oncogenic potential of iPSCs is further underscored by the findings that the critical tumor suppressor p53, known as the guardian of the genome, suppresses induced pluripotency. Therefore, the clinic application of iPSCs will require the optimization of the reprogramming technology to minimize the genetic and epigenetic abnormalities associated with induced pluripotency.
Animals
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Cellular Reprogramming
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Disease Models, Animal
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Epigenesis, Genetic
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Genomic Instability
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Humans
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Induced Pluripotent Stem Cells
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cytology
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metabolism
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Tumor Suppressor Protein p53
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metabolism
2.Cells derived from iPSC can be immunogenic - yes or no?
Jiani CAO ; Xiaoyan LI ; Xiao LU ; Chao ZHANG ; Honghao YU ; Tongbiao ZHAO
Protein & Cell 2014;5(1):1-3
The induced pluripotent stem cells (iPSCs), derived by ectopic expression of reprogramming factors in somatic cells, can potentially provide unlimited autologous cells for regenerative medicine. In theory, the autologous cells derived from patient iPSCs should be immune tolerant by the host without any immune rejections. However, our recent studies have found that even syngeneic iPSC-derived cells can be immunogenic in syngeneic hosts by using a teratoma transplantation model (Nature 474:212-215, 2011). Recently two research groups differentiated the iPSCs into different germ layers or cells, transplanted those cells to the syngeneic hosts, and evaluated the immunogenicity of those cells. Both of the two studies support our conclusions that some certain but not all tissues derived from iPSCs can be immunogenic, although they claimed either "negligible" or "lack of" immunogenicity in iPSC derivatives (Nature 494:100-104, 2013; Cell Stem Cell 12:407-412, 2013). To test the immunogenicity of clinically valuable cells differentiated from human iPSCs are emergently required for translation of iPSC technology to clinics.
Animals
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Cell Cycle Proteins
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metabolism
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Cell Transplantation
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methods
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Graft Rejection
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immunology
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Induced Pluripotent Stem Cells
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immunology
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transplantation
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Membrane Proteins
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metabolism
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Mice, Knockout
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Teratoma
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immunology
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metabolism
4.Cellular metabolism and homeostasis in pluripotency regulation.
Kun LIU ; Jiani CAO ; Xingxing SHI ; Liang WANG ; Tongbiao ZHAO
Protein & Cell 2020;11(9):630-640
Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
5.Oxidative phosphorylation safeguards pluripotency via UDP-N-acetylglucosamine.
Jiani CAO ; Meng LI ; Kun LIU ; Xingxing SHI ; Ning SUI ; Yuchen YAO ; Xiaojing WANG ; Shiyu LI ; Yuchang TIAN ; Shaojing TAN ; Qian ZHAO ; Liang WANG ; Xiahua CHAI ; Lin ZHANG ; Chong LIU ; Xing LI ; Zhijie CHANG ; Dong LI ; Tongbiao ZHAO
Protein & Cell 2023;14(5):376-381