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UrduBACKGROUND
AIM
To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles (EVs) influence anomalous cell junction and differentiation potential.
METHODS
We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation. Chromosomal karyotype analysis, flow cytometry, and immunofluorescent staining were utilized for hiPSC identification. Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential. Additionally, EVs were isolated from the supernatant, and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.
RESULTS
The generated hiPSCs, both with and without a MERTK mutation, exhibited normal karyotype and expressed pluripotency markers; however, hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential, as confirmed by transcriptomic and proteomic profiling. Furthermore, hiPSC-derived EVs were involved in various biological processes, including cell junction and differentiation.
CONCLUSION
HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential. Furthermore, hiPSC-derived EVs played a regulatory role in various biological processes, including cell junction and differentiation.
Key Words: Cell junction, Cellular differentiation, Extracellular vesicle, Human induced pluripotent stem cells, Transcriptomics, Proteomics
Core Tip: Patient-specific human induced pluripotent stem cell (hiPSC) technology is a valuable tool for disease modeling and the investigation of disease mechanisms, but altered biological properties caused by pathogenic genes may limit hiPSC applications. Through transcriptomics and proteomics, this study revealed cell junction abnormalities and aberrant cellular differentiation potential in hiPSCs with a MERTK mutation. Furthermore, the profiles of hiPSC-derived extracellular vesicles collected for transcriptomic and proteomic analysis indicated their involvement in the changes of biological characteristics occurring in hiPSCs.
- Citation: Zhang H, Wu LZ, Liu ZY, Jin ZB. Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential. World J Stem Cells 2024; 16(5): 512-524
- URL: https://www.wjgnet.com/1948-0210/full/v16/i5/512.htm
- DOI: https://dx.doi.org/10.4252/wjsc.v16.i5.512
