Attrition of X chromosome inactivation in aged hematopoietic stem cells
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)....
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
13 April 2021
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| In: |
Stem cell reports
Year: 2021, Volume: 16, Issue: 4, Pages: 708-716 |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2021.03.007 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.stemcr.2021.03.007 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2213671121001375 
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| Author Notes: | Ani Grigoryan, Johannes Pospiech, Stephen Krämer, Daniel Lipka, Thomas Liehr, Hartmut Geiger, Hiroshi Kimura, Medhanie A. Mulaw, and Maria Carolina Florian |
| Summary: | 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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| Physical Description: | Online Resource |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2021.03.007 |