Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells

被引：16

作者：

Grigoryan, Ani ^{[1
,14
,15
]}

Pospiech, Johannes ^{[1
]}

Kramer, Stephen ^{[2
,3
,4
,5
,6
,7
]}

Lipka, Daniel ^{[2
,3
]}

Liehr, Thomas ^{[8
]}

Geiger, Hartmut ^{[1
]}

Kimura, Hiroshi ^{[9
]}

Mulaw, Medhanie A. ^{[1
,10
]}

Florian, Maria Carolina ^{[1
,11
,12
,13
]}

机构：

[1] Univ Ulm, Inst Mol Med & Stem Cell Aging, Albert Einstein Allee 11c, D-89081 Ulm, Germany

[2] German Canc Res Ctr, Div Translat Med Oncol, Sect Translat Canc Epigen, Heidelberg, Germany

[3] Natl Ctr Tumor Dis NCT Heidelberg, Heidelberg, Germany

[4] German Canc Res Ctr, Bioinformat & Omics Data Anal, Heidelberg, Germany

[5] Heidelberg Univ, Fac Biosci, Heidelberg, Germany

[6] Univ Augsburg, Biomed Informat Data Min & Data Analyt, Fac Appl Comp Sci, Augsburg, Germany

[7] Univ Augsburg, Med Fac, Augsburg, Germany

[8] Friedrich Schiller Univ, Jena Univ Hosp, Inst Human Genet, Klinikum 1, D-07747 Jena, Germany

[9] Tokyo Inst Technol, Inst Innovat Res, Cell Biol Ctr, Midori Ku, 4259 Nagatsuta Cho, Yokohama, Kanagawa 2268503, Japan

[10] Univ Hosp Ulm, Dept Internal Med 1, Ulm, Germany

[11] Bellvitge Inst Biomed Res IDIBELL, Regenerat Med Program, Stem Cell Aging Grp, Av Gran Via 199-203, Barcelona 08908, Spain

[12] Program Adv Clin Translat Regenerat Med Catalonia, P CMR C, Av Gran Via 199-203, Barcelona 08908, Spain

[13] Ctr Networked Biomed Res Bioengn Biomat & Nanomed, Madrid, Spain

[14] Lund Univ, Lab Cell Tissue & Organ Engn, Dept Clin Sci, Wallenberg Ctr Mol Med, Solvegatan 19, S-22184 Lund, Sweden

[15] Lund Univ, Stem Cell Ctr, Solvegatan 19, S-22184 Lund, Sweden

来源：

STEM CELL REPORTS | 2021年 / 16卷 / 04期

关键词：

aging; ATACseq; chromatin accessibility; chromatin architecture; hematopoietic stem cell; HSC; LaminA/C; scRNAseq; X chromosome inactivation;

D O I：

10.1016/j.stemcr.2021.03.007

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 chro-mosome (Chr X) in aged HSCs. In summary, our data support the role of LaminA/C in the establishment of a special repressive compart-ment for XCI in HSCs, which is impaired upon aging.

引用

页码：708 / 716

页数：9

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