Acquired Genetic and Epigenetic Variation in Human Pluripotent Stem Cells

Area of Science:

• Stem cell biology
• Genomics
• Cellular and molecular medicine

Background:

• Human pluripotent stem cells (hPSCs) can accumulate non-random genomic variations during in vitro culture.
• Some acquired genomic alterations in hPSCs resemble those found in tumors and may confer a selective growth advantage.
• Reprogramming processes for human induced pluripotent stem cells (hiPSCs) may also introduce mutations.

Purpose of the Study:

• To highlight the challenge posed by genomic variation in hPSCs to clinical safety and research reliability.
• To discuss the importance of monitoring genomic integrity in hPSCs.
• To emphasize the need for optimizing hPSC culture and derivation protocols to minimize acquired genomic variation.

Main Methods:

• Review of existing methods for monitoring hPSC genomic integrity.
• Discussion on balancing practicality and sensitivity in method selection.
• Consideration of protocol adjustments for hPSC derivation and culture.

Main Results:

• Genomic variations in hPSCs can be non-random and similar to tumor-associated mutations.
• Reprogramming to create hiPSCs can introduce genetic mutations.
• Various methods exist for assessing hPSC genomic integrity, requiring careful selection based on application.

Conclusions:

• Genomic variation in hPSCs presents a significant concern for both clinical translation and basic research.
• Effective monitoring strategies and optimized culture conditions are essential for ensuring the genomic stability of hPSCs.
• Assessing the functional impact of detected genomic variations is increasingly critical with advancing detection technologies.