Projects per year
Abstract
Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling, thereby avoiding ethical issues arising from the use of embryo-derived cells. However, despite clear similarities between the two cell types, it is likely they are not identical. In this study we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors. We find that while hESCs and hiPSCs express a near identical set of proteins, they show consistent quantitative differences in the expression levels of a wide subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs. The proteomic data show hiPSCs have significantly increased abundance of vital cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins, which correlated with phenotypic differences between hiPSCs and hESCs. Thus, higher levels of glutamine transporters correlated with increased glutamine uptake, while higher levels of proteins involved in lipid synthesis correlated with increased lipid droplet formation. Some of the biggest metabolic changes were seen in proteins involved in mitochondrial metabolism, with corresponding enhanced mitochondrial potential, shown experimentally using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins including ECM components and growth factors, some with known tumorigenic properties as well as proteins involved in the inhibition of the immune system. Our data indicate that reprogramming of human fibroblasts to iPSCs effectively restores protein expression in cell nuclei to a similar state to hESCs, but does not similarly restore the profile of cytoplasmic and mitochondrial proteins, with consequences for cell phenotypes affecting growth and metabolism. The data improve understanding of the molecular differences between induced and embryonic stem cells with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications.
Original language | English |
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Publisher | BioRxiv |
Number of pages | 34 |
DOIs | |
Publication status | Published - 19 Aug 2023 |
Keywords
- proteomics
- iPSC
- mass spectrometry
- hESC
- TMT
- stem cells
- protein content
Fingerprint
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Harnessing the splicing code for targeted control of gene expression (UNLEASH)
Gray, D. (Investigator) & Lamond, A. (Investigator)
1/06/23 → 31/05/29
Project: Research
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Molecular Analysis of Nuclear Bodies and RNP Trafficking Pathways in the Cell Nucleus (Joint with the University of Oslo)
Lamond, A. (Investigator)
Biotechnology and Biological Sciences Research Council
1/05/21 → 30/04/25
Project: Research
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The Interplay Between Oxygen Sensors PHDs and the Cell Cycle (Joint with University of Liverpool)
Fleming, S. (Investigator), Lamond, A. (Investigator) & Swedlow, J. (Investigator)
1/09/17 → 31/08/24
Project: Research
Research output
- 1 Article
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Proteomic and functional comparison between human induced and embryonic stem cells
Brenes Murillo, A., Griesser, E., Sinclair, L., Davidson, L., Prescott, A., Singh, F., Hogg, E., Espejo-Serrano, C., Jiang, H., Yoshikawa, H., Platani, M., Swedlow, J., Findlay, G., Cantrell, D. & Lamond, A. (Lead / Corresponding author), 2024, In: eLife. p. 1-32 32 p.Research output: Contribution to journal › Article › peer-review
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