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Temporal Profiling of Epitranscriptomic Modulators during Osteogenic Differentiation of Human Embryonic Stem Cells

Jiekai Yin1, Tianyu F Qi1, Yen-Yu Yang2

  • 1Environmental Toxicology Graduate Program, University of California Riverside, Riverside, California 92521-0403, United States.

Journal of Proteome Research
|June 22, 2023
PubMed

Insights

This study reveals that RNA modification proteins (RWEs) are crucial for bone formation (osteogenesis). Many RWEs decrease during osteogenesis, suggesting their regulatory role in this process.

Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Osteogenesis involves complex regulatory networks.
  • RNA modifications and their associated proteins (RWEs) regulate biological processes.
  • The role of RWEs in osteogenesis remains largely unexplored.

Purpose of the Study:

  • To comprehensively profile epitranscriptomic RWE proteins during human embryonic stem cell (ESC) osteogenic differentiation.
  • To investigate the potential regulatory functions of RWEs in osteogenesis.

Main Methods:

  • Quantitative assessment of 154 epitranscriptomic RWE proteins using LC-MS/MS in parallel-reaction monitoring (PRM) mode.
  • Analysis of protein-protein interactions (PPI) and gene set enrichment (GSEA) using RNA-seq data.

Main Results:

  • Approximately 50% of detected RWEs were down-regulated during osteogenic differentiation.
  • Down-regulated RWEs were primarily involved in RNA methylation and pseudouridylation.
  • PPI network analysis indicated associations between down-regulated RWEs and osteogenesis-related proteins.
  • GSEA suggested a potential role for METTL1 in osteogenesis via the cytokine network.

Conclusions:

  • This is the first study to profile epitranscriptomic RWEs during human ESC osteogenesis.
  • The findings highlight potential regulatory roles of RWEs in osteogenesis.
  • Specific RWEs, like METTL1, may be key players in bone formation through cytokine signaling.
Keywords:
RNA modificationsdifferentiationepitranscriptomicsosteogenesisparallel-reaction monitoringstem cellstargeted proteomics

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