Proteomic and functional comparison between human induced and embryonic stem cells.

Autor: Brenes AJ; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.; Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.; Human Pluripotent Stem Cell Facility, School of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, Dundee, United Kingdom., Griesser E; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Sinclair LV; Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Davidson L; Human Pluripotent Stem Cell Facility, School of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, Dundee, United Kingdom., Prescott AR; Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Singh F; MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Hogg EKJ; MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Espejo-Serrano C; MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Jiang H; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Yoshikawa H; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Platani M; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Swedlow JR; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Findlay GM; MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Cantrell DA; Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Lamond AI; Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Jazyk: angličtina
Zdroj: ELife [Elife] 2024 Nov 14; Vol. 13. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.7554/eLife.92025
Abstrakt: 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. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors and find that while they express a near-identical set of proteins, they show consistent quantitative differences in the abundance of a subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs, with increased abundance of cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins. Prominent changes detected in proteins involved in mitochondrial metabolism correlated with enhanced mitochondrial potential, shown using high-resolution respirometry. hiPSCs also produced higher levels of secreted proteins, including growth factors and proteins involved in the inhibition of the immune system. The data indicate that reprogramming of fibroblasts to hiPSCs produces important differences in cytoplasmic and mitochondrial proteins compared to hESCs, with consequences affecting growth and metabolism. This study improves our understanding of the molecular differences between hiPSCs and hESCs, with implications for potential risks and benefits for their use in future disease modelling and therapeutic applications.
Competing Interests: AB, LS, LD, AP, FS, EH, CE, HJ, HY, GF, DC No competing interests declared, EG Now works for Boehringer Ingelheim Pharma GmbH & Co KG, MP Board member of Tartan Cell Technologies Ltd, JS Board member of Tartan Cell Technologies Ltd and Glencoe Software Ltd, AL Board member of Tartan Cell Technologies Ltd and Platinum Informatics Ltd
(© 2024, Brenes et al.)
Databáze: MEDLINE