Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation

Djeghloul, Dounia; Kuranda, Klaudia; Kuzniak, Isabelle; Barbieri, Daniela; Naguibneva, Irina; Choisy, C.; Borie, Raphaël; Dosquet, Christine; Pla, Marika; Vanneaux, Valérie; Socié, Gérard; Porteu, Françoise; Garrick, David; Goodhardt, Michèle

doi:10.1016/j.stemcr.2016.05.007

Cited by 90 publications

(91 citation statements)

References 57 publications

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“…Recently, some noncoding RNAs have been demonstrated to play important roles in HSC functions, and their expression levels change with age. Djeghloul et al observed that the expression of micro-RNA miR-125b increased with age in human HSCs [95]. These authors also found that inhibition of miR-125 improved the capacity of HSCs from elderly individuals to generate B cells.…”

Section: Noncoding Rnasmentioning

confidence: 94%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.

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Section: Noncoding Rnasmentioning

confidence: 94%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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“…H3K9me3 is a histone modification critical for heterochromatin maintenance and has been shown to protect DNA from double strand breaks (107). Thus, the age-associated decline of this histone methyltransferase could also contribute to the accrual of DNA damage due to genome instability (108). It is likely that as more information about epigenetic regulation in HSCs is revealed, more connections between histone modifications and age-associated DNA damage accrual will also be established.…”

Section: Drivers Of Dna Damagementioning

confidence: 99%

Accumulation of DNA damage in the aged hematopoietic stem cell compartment

Beerman

2017

Seminars in Hematology

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Aging is associated with loss of functional potential of multiple tissue systems, and there has been significant interest in understanding how tissue specific cells contribute to this decline. DNA damage accumulation has been widely associated with aging in differentiated cell types. However, tissue specific stem cells were once thought to be a geno-protected population, as damage accrued in a stem cell population has the potential to be inherited by differentiated progeny as well as propagated within the stem cell compartment through self-renewal divisions. This review will discuss the evidence for DNA damage accumulation in the aged HSC compartment, potential drivers, and finally the consequences of the acquired damage.

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“…We first assessed the spatial distribution of histone H3 lysine 9 trimethylation (H3K9me3), as a marker of constitutive heterochromatin (Becker et al, 2016) (Bannister et al, 2001). In freshly isolated HSCs, and in lymphoid progenitors, H3K9me3 was homogeneously distributed along the entire peripheral margin of the nucleus ( Figure 4A), as previously described (Djeghloul et al, 2016;Ugarte et al, 2015). By contrast, in freshly isolated myeloid progenitors, H3K9me3 distribution was more heterogeneous: foci were detected in the nucleoplasm, and at the peripheral margin of the nucleus, the density of H3K9me3 foci was lower in the invaginated regions than the other (convex) regions ( Figure 4A).…”

Section: Resultsmentioning

confidence: 97%

Microtubules deform the nucleus and force chromatin reorganization during early differentiation of human hematopoietic stem cells

Biedzinski

Faivre²,

Vianay

et al. 2019

Preprint

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Hematopoietic stem cells (HSC) can differentiate into all hematopoietic lineages to support hematopoiesis. Cells from the myeloid and lymphoid lineages fulfill distinct functions with specific shapes and intra-cellular architectures. The role of cytokines in the regulation of HSC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here we show that large invaginations are generated by microtubule constraints on the swelling nucleus of human HSCs during early commitment toward the myeloid lineage. These invaginations are associated with chromatin reorganization, local loss of H3K9 trimethylation and changes in expression of specific hematopoietic genes. This establishes the role of microtubules in defining the unique lobulated nuclear shape observed in myeloid progenitor cells and suggests that this shape is important to establish the gene expression profile specific to this hematopoietic lineage. It opens new perspectives on the implications of microtubule-generated forces, in the early specification of the myeloid lineage.

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Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation

Cited by 90 publications

References 57 publications

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Accumulation of DNA damage in the aged hematopoietic stem cell compartment

Microtubules deform the nucleus and force chromatin reorganization during early differentiation of human hematopoietic stem cells

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