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Proteomic and functional comparison between human induced and embryonic stem cells
Alejandro J Brenes1,2,3, Eva Griesser1, Linda V Sinclair2
1Molecular, Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
Elife
|November 14, 2024
Summary
Human induced pluripotent stem cells (hiPSCs) show distinct protein profiles compared to human embryonic stem cells (hESCs). These differences in cytoplasmic and mitochondrial proteins impact growth and metabolism, with implications for regenerative medicine.
Area of Science:
- Stem cell biology
- Proteomics
- Cellular metabolism
Background:
- Human induced pluripotent stem cells (hiPSCs) offer potential alternatives to human embryonic stem cells (hESCs) for regenerative medicine and disease modeling.
- Understanding the molecular distinctions between hiPSCs and hESCs is crucial for their safe and effective therapeutic applications.
Purpose of the Study:
- To characterize and compare the proteomes of hiPSC and hESC lines.
- To identify quantitative differences in protein abundance between hiPSCs and hESCs.
- To investigate the functional consequences of proteomic differences on cellular growth and metabolism.
Main Methods:
- Proteomic analysis of multiple hiPSC and hESC lines from independent donors.
- Quantitative mass spectrometry to determine protein abundance.
- High-resolution respirometry to assess mitochondrial function.
Main Results:
- hiPSCs and hESCs express largely identical protein sets but exhibit consistent quantitative differences in specific proteins.
- hiPSCs demonstrate increased total protein content, with higher abundance of cytoplasmic and mitochondrial proteins, including nutrient transporters and metabolic enzymes.
- Enhanced mitochondrial metabolism and increased secretion of growth factors and immunomodulatory proteins were observed in hiPSCs.
- Reprogramming fibroblasts to hiPSCs results in significant alterations in cytoplasmic and mitochondrial protein composition, affecting cellular growth and metabolism.
Conclusions:
- Reprogramming to hiPSCs induces notable changes in protein expression, particularly in cytoplasmic and mitochondrial compartments, compared to hESCs.
- These proteomic alterations in hiPSCs have functional consequences for cellular growth, metabolism, and immune interactions.
- The findings enhance the understanding of molecular differences between hiPSCs and hESCs, informing their potential risks and benefits in future therapeutic and disease modeling applications.
