Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells.
Stem Cell Reports
; 16(4): 708-716, 2021 04 13.
Article
in En
| MEDLINE
| ID: mdl-33798450
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Cellular Senescence
/
X Chromosome Inactivation
Limits:
Animals
/
Humans
Language:
En
Journal:
Stem Cell Reports
Year:
2021
Document type:
Article
Affiliation country:
Germany