Aging of the hematopoietic stem cells niche

Nakamura‐Ishizu, Ayako; Suda, Toshio

doi:10.1007/s12185-014-1641-8

Cited by 29 publications

(16 citation statements)

References 98 publications

(103 reference statements)

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“…Such alterations in the aged BM niche have led to the speculation that these changes might also play a role in the development of haematological malignancies [15], which are often age-related; this is supported by the observation that a pre-leukaemic cell line showed preferential growth in aged BM [28]. In another study by the same authors, they showed that transplantation of transformed HSC clones developed preferentially in the aged BM microenvironment in comparison to the young BM niche [29].…”

Section: The Aged Bone Marrow Nichementioning

confidence: 96%

Immune senescence: significance of the stromal microenvironment

Masters

Haynes

et al. 2016

Clinical and Experimental Immunology

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SummaryThe immune system undergoes age-associated changes known as immunosenescence, resulting in increased susceptibility to infections, cancers and autoimmunity in the aged. The basis of our understanding of immunosenescence has been derived primarily from studies examining intrinsic defects within many of the cells of the immune system. While these studies have provided insight into the mechanisms of immunosenescence, a picture is now emerging that the stromal microenvironment within lymphoid organs also contributes significantly to the age-associated decline of immune function. These extrinsic defects appear to impact the functional activity of immune cells and may offer a potential target to recover immune activity. Indeed, rejuvenation studies which have targeted the stromal niche have restored immune function in aged successfully, highlighting the impact of the microenvironment towards the aetiology of immunosenescence.

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Section: The Aged Bone Marrow Nichementioning

confidence: 96%

Immune senescence: significance of the stromal microenvironment

Masters

Haynes

et al. 2016

Clinical and Experimental Immunology

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“…The alterations noted in aged hematopoietic stem cells were until recently thought to be a consequence of cell-intrinsic modifications (65,66). Nevertheless, new data the important role of multiple extrinsic factors in driving hematopoietic stem cell aging (67). Zhou and colleagues investigated the importance of adipocyte-derived stem cell factor in genotoxic insults in the bone marrow (19).…”

Section: Perspectives / Future Directionsmentioning

confidence: 99%

Adipocytes role in the bone marrow niche

et al. 2017

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Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell function. Recently, Zhou et al. (2017) by using state-of-the-art techniques, including sophisticated Cre/loxP technologies, confocal microscopy, in vivo lineage-tracing, flow cytometry, and bone marrow transplantation, reveal that adipocytes promote hematopoietic recovery after irradiation. This study challenges the current view of adipocytes as negative regulators of the hematopoietic stem cells niche, and reopens the discussion about adipocytes’ roles in the bone marrow. Strikingly, genetic deletion of stem cell factor specifically from adipocytes leads to deficiency in hematopoietic stem cells, and reduces animal survival after myeloablation, The emerging knowledge from this research will be important for the treatment of multiple hematologic disorders.

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“…* Atsushi Hirao ahirao@staff.kanazawa-u.ac.jp 1 Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan ability of regulatory transcription machinery proteins to access the chromatin of genomic DNA, thereby controlling gene expression. In particular, Polycomb group (PcG) proteins contribute to self-renewal of HSCs by repressing genes involved in differentiation.…”

Section: Epigenetic and Metabolic Regulation In Hematopoiesis/ Leukemmentioning

confidence: 99%

“…Acetylation, methylation, and phosphorylation of histones change the Hematopoietic stem cells (HSCs) are defined as cells that have the ability to perpetuate undifferentiated status through self-renewal and to develop into mature cells through differentiation. Fine-tuning of self-renewal and differentiation programs, mediated by cooperative networks of intrinsic and extrinsic factors, contributes to stem cell homeostasis in vivo [1,2]. Accumulating evidence has revealed the presence of "stemness" signals; that is, molecules and signaling pathways that play critical roles in maintaining the undifferentiated properties of HSCs.…”

mentioning

confidence: 99%

Guest editorial: Cooperative networks for stem cell homeostasis in normal and malignant hematopoiesis: from metabolism to epigenetics

Hirao

2016

Int J Hematol

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of HSCs in vivo are quiescent, even though cytokines known to regulate HSCs, such as c-Kit and mpl ligand, are considered to be growth factors that stimulate cell cycle progression. How such factors maintain quiescent HSCs is still a mystery. Presumably, direct interactions of the HSCs with neighboring cells (niche cells); secreted factors such as nutrients, hormones, and metabolites; or oxygen tension modulate the signals of growth factors in the HSCs.In the niche, extrinsic factors coordinate multiple processes that are essential for HSC homeostasis and are mediated by metabolic regulation. Several studies have suggested that HSCs utilize glycolysis, whereas oxidative phosphorylation becomes dominant in progenitors. Like HSCs, LSCs exhibit low levels of ROS; however, unlike HSCs they appear to have low glycolytic flow, indicating that there are critical differences in metabolic regulation between these cell types. In this issue, Jiang et al. argue that knowledge of the molecular mechanisms of metabolic regulation mediated by key molecules, e.g., HIF1/2, AMPK, and mTOR, will provide novel therapeutic approaches for eradiation of LSCs [3].Multistep processes of hematopoiesis and leukemogenesis are controlled by epigenetics, which regulates gene expression by increasing or decreasing DNA methylation or post-translational modifications of histone core proteins. DNA methylation proceeds by the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs). DNA demethylation by DNA hydroxylase TET enzymes is a critical process for reversing this methylation. The article by Celik et al. discusses recent studies showing that the cooperative regulation of these DNA methylation enzymes is critical for hematopoiesis and leukemogenesis [4]. Acetylation, methylation, and phosphorylation of histones change the Hematopoietic stem cells (HSCs) are defined as cells that have the ability to perpetuate undifferentiated status through self-renewal and to develop into mature cells through differentiation. Fine-tuning of self-renewal and differentiation programs, mediated by cooperative networks of intrinsic and extrinsic factors, contributes to stem cell homeostasis in vivo [1,2]. Accumulating evidence has revealed the presence of "stemness" signals; that is, molecules and signaling pathways that play critical roles in maintaining the undifferentiated properties of HSCs. Common mechanisms may regulate stemness in HSCs and leukemias: although leukemia stem cells (LSCs) appear to be heterogeneous, their gene expression profiles closely resemble those of normal HSCs or progenitors. Understanding the commonalities and critical differences between HSCs and LSCs in the regulation of stemness is required to find the therapeutic window. In this issue, four articles review the physiological and pathophysiological roles of metabolism and epigenetic regulation in hematopoiesis. The articles include current basic knowledge and recent topics in...

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Aging of the hematopoietic stem cells niche

Cited by 29 publications

References 98 publications

Immune senescence: significance of the stromal microenvironment

Immune senescence: significance of the stromal microenvironment

Adipocytes role in the bone marrow niche

Guest editorial: Cooperative networks for stem cell homeostasis in normal and malignant hematopoiesis: from metabolism to epigenetics

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