Colony morphology altered by Myh9 deficiency uncoupled from pluripotency

The naïve mouse embryonic stem cells, characterized by high nuclear/cytoplasmic ratio, and dome-shaped colonies with smoothly contoured edges, exhibit self-renewal and pluripotency. However, it is unclear about the biological significance of dome-like morphology in relation to pluripotency. Here, we generate stable ES cell lines with a flat morphology, capable of sustained monolayer growth and efficient single-cell clonogenic capacity, by knocking out non-muscle myosin heavy chain IIA. Notably, even when deprived of the typical dome-like colony morphology, the ES cells retain their self-renewal capacity and pluripotency to differentiate into the three germ layers. Our data disprove the long-standing paradigm in stem cell field that the dome-shaped colony architecture is intrinsically linked to naïve pluripotency, instead demonstrating that core pluripotency circuitry operates independently of this morphological constraint. Overall design: We analyzed the transcriptome in mESCs upon Myh9 deficiency.