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Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic

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Abstract

The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure.

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Data Availability

The raw data of proteomics are available on the CCMS-MassIVE (accession No. MassIVE MSV000092902) online data repository. The raw data are available in the repository of the Institute on its server, and with the corresponding author too.

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Acknowledgements

Dr Renu Negi is grateful to CSIR-UGC, New Delhi, for providing Research Fellowship. The authors are grateful to Ms Deepshikha Srivastava, Technical Officer, LC-MS/MS Laboratory, and Mr Jai Shankar, Technical Officer, Microscope Laboratory, Central Instrumentation Facility, CSIR-Indian Institute of Toxicology Research, Lucknow, India, for extending the operational support for LC-MS/MS during proteomics studies and Transmission Electron Microscopic study.

Funding

The research was funded by the Indian Council of Medical Research (ICMR), New Delhi, India (Grant Sanction number: 5/4–5/3/9/DHR/Neuro/2021/NCD-1 dated 30/03/2022).

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  1. R. Negi, A. Srivastava, and A. K. Srivastava contributed equally to this work

Authors and Affiliations

  1. Systems Toxicology Group, CSIR-Indian Institute of Toxicology Research Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, P.O. Box No. 80, Lucknow, 226 001, Uttar Pradesh, India

    R. Negi, A. K. Srivastava, P. Vatsa, U. A. Ansari, B. Khan, H. Singh, A. Pandeya & AB Pant

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India

    R. Negi, P. Vatsa, U. A. Ansari & AB Pant

  3. Department of Biochemistry, University of Lucknow, Lucknow, Uttar Pradesh, 226007, India

    A. Srivastava

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Contributions

ABP has conceptualized the research work, designed the protocols, acquired the funds, project administration work, supervised throughout experimentations, and reviewed and edited the manuscript. RN, AS, and AKS performed the experiments, data curation, and analysis and prepared the original draft of the manuscript. PV and UAA helped with the data analysis writing and editing of the manuscript. BK and HS assisted in carrying out the parts of the Open Array and Real-Time PCR experiments. AP helps in the investigation, formal analysis, and visualization of the data.

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Correspondence to AB Pant.

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Negi, R., Srivastava, A., Srivastava, A.K. et al. Proteomic-miRNA Biomics Profile Reveals 2D Cultures of Human iPSC-Derived Neural Progenitor Cells More Sensitive than 3D Spheroid System Against the Experimental Exposure to Arsenic. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03924-z

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  • DOI: https://doi.org/10.1007/s12035-024-03924-z

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