Susanna Teppo
sustep.bsky.social
Susanna Teppo
@sustep.bsky.social
Bioscientist (PhD) | Molecular Biology | Biomedicine | STEM teacher
Highlighting the latest advancements in stem cell biology and regenerative medicine.
How do you address genomic instability in your hPSC cultures?

Direct links to the publications:
Krivec et al. 2024 Nature - Cell Death & Disease: doi.org/10.1038/s414...
Stavish et al. 2024 Stem Cell Reports: doi.org/10.1016/j.st...
Jacobs et al. 2016 Stem Cell Reports: doi.org/10.1016/j.st...
Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity - Cell Death & Disease
Cell Death & Disease - Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity
doi.org
November 24, 2024 at 3:43 PM
How do we best ensure genomic stability while culturing on defined and xeno-free conditions?

Jacobs et al. (2016) provided practical insights especially for high-density cultures:
• Cultures on full-length laminin-521 exhibited reduced DNA damage
• Frequent medium changes rescued genomic integrity
Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity - Cell Death & Disease
Cell Death & Disease - Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity
doi.org
November 24, 2024 at 3:43 PM
Impact of culture conditions – how to prevent instability?

Recently, Stavish et al. (2024) suggested that 1q-gained cells can only take over the culture when the cells are cultured on feeder-free conditions (such as E8/VTN).
Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity - Cell Death & Disease
Cell Death & Disease - Gain of 1q confers an MDM4-driven growth advantage to undifferentiated and differentiating hESC while altering their differentiation capacity
doi.org
November 24, 2024 at 3:43 PM
Elevated levels of MDM4 (in 1q) inhibit p53-mediated apoptosis, allowing damaged 1q-gained cells to persist and outcompete genetically balanced cells.

Krivec and colleagues show that 1q-gained hPSCs can also take over during differentiation and result in more immature hepatocytes and cardiomyocytes
November 24, 2024 at 3:43 PM