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The fate of the X chromosome in cells differentiated from female human embryonic stem
cell (hESC) lines remains controversial. Patel et al. analyze the X chromosome state
of numerous hESC lines during derivation, propagation, and differentiation. They establish
a hierarchy of X states in hESCs and find that the X chromosome state pre-existing
in hESCs is maintained during differentiation.
Here, the scientists demonstrate that X chromosome dosage compensation is not required for ESC differentiation. Their data imply that XiXIST+Xa ESCs are most suited for downstream applications and show that all other X states are abnormal byproducts of their ESC derivation and propagation method.