Reprogrammed Cells Display Distinct Proteomic Signatures Associated with Colony Morphology Variability
Yngvild Bjørlykke1,2, Anne M Søviknes1, Laurence Hoareau1
1Department of Clinical Science, University of Bergen, Bergen, Norway.
Stem Cells International
|December 13, 2019
Summary
Stable human induced pluripotent stem cells (hiPSCs) show distinct proteomic profiles linked to consistent colony morphology. Unstable hiPSC lines exhibit epithelial to mesenchymal transition markers and reduced differentiation capacity, impacting their pluripotency.
Area of Science:
- Stem cell biology
- Proteomics
- Cellular differentiation
Background:
- Human induced pluripotent stem cells (hiPSCs) are crucial for regenerative medicine due to their differentiation potential.
- Maintaining hiPSC pluripotency and stable undifferentiated states is essential for reliable cell therapies.
- Spontaneous differentiation and phenotypic instability in hiPSC lines hinder their clinical application.
Purpose of the Study:
- To investigate the proteomic differences between stable and unstable hiPSC colony morphologies.
- To identify molecular markers predicting hiPSC stability and differentiation capacity.
- To understand the regulatory pathways involved in hiPSC phenotypic instability.
Main Methods:
- Proteomic analysis of 20 hiPSC lines classified as stable or unstable based on colony morphology.
- Comparison of pluripotency and epithelial to mesenchymal transition (EMT) protein markers.
- Bioinformatic prediction of key signaling pathways regulating hiPSC stability.
- Assessment of spontaneous and directed differentiation capacity in hiPSC lines.
Main Results:
- Distinct proteomic signatures were identified for stable and unstable hiPSC colonies, despite similar expression of core pluripotency markers (POU5F1, SOX2).
- Unstable hiPSC lines showed enrichment of EMT markers and predicted involvement of the transforming growth factor beta (TGFB) signaling pathway.
- Specific proteins were identified that effectively distinguish between stable and unstable hiPSC states.
- Unstable hiPSC lines exhibited significantly reduced capacity for both spontaneous embryonic body formation and directed differentiation.
Conclusions:
- Colony morphology in hiPSCs is associated with distinct proteomic profiles and functional differentiation capacity.
- Proteomic analysis can reveal underlying molecular mechanisms driving hiPSC instability.
- Identifying markers of hiPSC stability is crucial for selecting suitable cell lines for research and therapeutic applications.
