Breaking the link between morphology and potency for mESCs

BACKGROUND: In stem cell biology, a long-held structure-function relationship is the domed colony morphology and naïve pluripotency for mouse or human pluripotent stem cells. This link has provided a convenient way to recognize bona fide naïve pluripotent cells during derivation, passaging and characterization. However, the molecular basis of this link remains poorly understood. RESULTS: We show that a loss of domed morphology may not impact the overall genetic architecture of naïve pluripotency in mouse embryonic stem cells (mESCs). We first generated stable mESC lines by knocking out Myh9 that encodes non-muscle myosin heavy chain IIA, resulting in colonies deprived of the typical domed morphology, but competent to differentiate into the three germ layers and chimeric mice. Modulating cell morphologies with inhibitors against kinases known to regulate myosin pathway also phenocopy the knockout in wild type mESCs. CONCLUSIONS: These results provide evidence that the domed morphology and potency can be uncoupled and suggest that domed structure is not a pre-requisite for acquiring and maintaining naïve pluripotency.