During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the periphery of the nucleus. Beside X chromosome reactivation resulting in a highly penetrant aging-like hematopoietic malignancy, little is known about XCI in aged hematopoietic stem cells (HSCs) . Here, we demonstrate that LaminA/C defines a distinct repressive nuclear compartment for XCI in young HSCs, and its reduction in aged HSCs correlates with an impairment in the overall...