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 [PMID: 38817331 DOI: 10.4252/wjsc.v16.i5.512]
Corresponding Author of This Article
Zi-Bing Jin, MD, PhD, Research Scientist, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomin Lane, Dongcheng District, Beijing 100730, China. jinzb502@ccmu.edu.cn
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. May 26, 2024; 16(5): 512-524 Published online May 26, 2024. doi: 10.4252/wjsc.v16.i5.512
Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential
Hang Zhang, Ling-Zi Wu, Zhen-Yu Liu, Zi-Bing Jin
Hang Zhang, Ling-Zi Wu, Zhen-Yu Liu, Zi-Bing Jin, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
Co-first authors: Hang Zhang and Ling-Zi Wu.
Author contributions: Zhang H and Wu LZ contributed equally to this work. Zhang H and Jin ZB designed experiments and drafted the manuscript; Zhang H and Liu ZY performed experiments; Zhang H and Wu LZ analyzed and interpreted data; Jin ZB conceived the study, supervised the project, revised the manuscript and provided the financial support; and the manuscript was approved by all authors.
Supported bythe National Natural Science Foundation of China, No. 82125007; and Beijing Natural Science Foundation, No. Z200014.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (Approval No. TRECKY2021-088).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data needed to evaluate the conclusions in the paper are present in the paper and the supplementary materials. The RNA-seq and proteomics data reported in this paper are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zi-Bing Jin, MD, PhD, Research Scientist, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomin Lane, Dongcheng District, Beijing 100730, China. jinzb502@ccmu.edu.cn
Received: December 13, 2023 Revised: January 29, 2024 Accepted: April 1, 2024 Published online: May 26, 2024 Processing time: 162 Days and 23.2 Hours
Abstract
BACKGROUND
Human induced pluripotent stem cell (hiPSC) technology is a valuable tool for generating patient-specific stem cells, facilitating disease modeling, and investigating disease mechanisms. However, iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.
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.
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.
