Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

ABSTRACT: Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that ove

SUBMITTER: Stavish D 

PROVIDER: S-EPMC11368687 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature