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How Does Reprogramming to Pluripotency Affect Genomic Imprinting?

Valentina Perrera1, Graziano Martello1

  • 1Department of Molecular Medicine, School of Medicine and Surgery, University of Padova, Padua, Italy.

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Summary
This summary is machine-generated.

Human induced Pluripotent Stem Cells (hiPSCs) can develop into various cell types for regenerative medicine. This review highlights epigenetic errors, specifically loss of imprinting in hiPSCs, which are linked to developmental disorders and cancer.

Keywords:
IPSepigeneticsimprintingpluripotencyreprogrammingstem cells

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Area of Science:

  • Epigenetics and Stem Cell Biology
  • Genomic Imprinting
  • Regenerative Medicine

Background:

  • Human induced Pluripotent Stem Cells (hiPSCs) are valuable for regenerative medicine, disease modeling, and drug screening.
  • Genomic aberrations, including DNA mutations, can arise during hiPSC derivation.
  • Epigenetic integrity, particularly genomic imprinting, is crucial for hiPSC function and safety.

Purpose of the Study:

  • To review the epigenetic aberrations in hiPSCs, focusing on genomic imprinting.
  • To discuss the implications of loss of imprinting in hiPSCs for human pathologies.
  • To suggest strategies for detecting and avoiding epigenetic abnormalities in hiPSCs.

Main Methods:

  • Review of existing literature on hiPSC derivation and epigenetic analysis.
  • Focus on genomic imprinting as a key epigenetic mechanism.
  • Analysis of DNA methylation patterns at imprinted loci in hiPSCs.

Main Results:

  • Conventional hiPSCs exhibit global hypermethylation but loss of methylation at imprinted loci.
  • Naïve hiPSCs show global hypomethylation and widespread loss of methylation at imprinted loci.
  • Loss of imprinting in hiPSCs is associated with developmental disorders and cancer.

Conclusions:

  • Ensuring correct epigenetic information, especially imprinting, is critical for safe hiPSC applications.
  • Specific imprinted genes associated with pathologies are frequently misregulated in hiPSCs.
  • Strategies are needed to detect and prevent undesirable epigenetic abnormalities in hiPSCs.