Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Apr 2

PMID 33798450

Citations 10

Authors

Ani Grigoryan

Johannes Pospiech

Stephen Kramer

Daniel Lipka

Thomas Liehr

Hartmut Geiger

Hiroshi Kimura

Medhanie A Mulaw

Maria Carolina Florian

Affiliations

Soon will be listed here.

Abstract

During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the nuclear periphery. 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 control of XCI. Integrated omics analyses reveal higher variation in gene expression, global hypomethylation, and significantly increased chromatin accessibility on the X chromosome (Chr X) in aged HSCs. In summary, our data support the role of LaminA/C in the establishment of a special repressive compartment for XCI in HSCs, which is impaired upon aging.

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