Breaking the link between morphology and potency for mESCs

Area of Science:

• Stem Cell Biology
• Developmental Biology
• Cell Morphology

Background:

• A common belief in stem cell biology links domed colony morphology to naïve pluripotency in mouse and human pluripotent stem cells.
• This structure-function relationship aids in identifying naïve pluripotent cells but lacks a clear molecular explanation.

Purpose of the Study:

• To investigate the molecular basis of the link between domed morphology and naïve pluripotency in mouse embryonic stem cells (mESCs).
• To determine if domed morphology is a prerequisite for maintaining naïve pluripotency and differentiation potential.

Main Methods:

• Generated stable mESC lines with knocked-out Myh9 gene, encoding non-muscle myosin heavy chain IIA, to eliminate domed morphology.
• Utilized kinase inhibitors targeting the myosin pathway to modulate cell morphology in wild-type mESCs.

Main Results:

• mESC lines lacking Myh9 exhibited altered morphology but retained the capacity for three germ layer differentiation.
• These modified mESCs were capable of forming chimeric mice, indicating maintained pluripotency.
• Pharmacological inhibition of myosin pathway kinases mimicked the knockout phenotype in wild-type mESCs.

Conclusions:

• Domed morphology and pluripotency can be uncoupled in mouse embryonic stem cells.
• The study suggests that a domed structure is not essential for the acquisition or maintenance of naïve pluripotency.