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Cells Dec 2020Fibronectin is a ubiquitous extracellular matrix protein that is produced by many cell types in the bone marrow and distributed throughout it. Cells of the stem cell... (Review)
Review
Fibronectin is a ubiquitous extracellular matrix protein that is produced by many cell types in the bone marrow and distributed throughout it. Cells of the stem cell niche produce the various isoforms of this protein. Fibronectin not only provides the cells a scaffold to bind to, but it also modulates their behavior by binding to receptors on the adjacent hematopoietic stem cells and stromal cells. These receptors, which include integrins such as α4β1, α9β1, α4β7, α5β1, αvβ3, Toll-like receptor-4 (TLR-4), and CD44, are found on the hematopoietic stem cell. Because the knockout of fibronectin is lethal during embryonal development and because fibronectin is produced by almost all cell types in mammals, the study of its role in hematopoiesis is difficult. Nevertheless, strong and direct evidence exists for its stimulation of myelopoiesis and thrombopoiesis using in vivo models. Other reviewed effects can be deduced from the study of fibronectin receptors, which showed their activation modifies the behavior of hematopoietic stem cells. Erythropoiesis was only stimulated under hemolytic stress, and mostly late stages of lymphocytic differentiation were modulated. Because fibronectin is ubiquitously expressed, these interactions in health and disease need to be taken into account whenever any molecule is evaluated in hematopoiesis.
Topics: Animals; Cell Differentiation; Cell Movement; Cell Proliferation; Erythropoiesis; Fibronectins; Hematopoiesis; Hematopoietic Stem Cells; Hemolysis; Humans; Hyaluronan Receptors; Integrins; Mice; Myelopoiesis; Receptors, Fibronectin; Stem Cell Niche; Stem Cells; Thrombopoiesis; Toll-Like Receptor 4
PubMed: 33353083
DOI: 10.3390/cells9122717 -
European Heart Journal Apr 2016Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium... (Review)
Review
Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis.
Topics: Atherosclerosis; Blood Platelets; Cholesterol; Hematopoiesis; Hematopoiesis, Extramedullary; Hematopoietic Stem Cells; Humans; Leukocytosis; Metabolic Diseases; Monocytes; Myelopoiesis; Myeloproliferative Disorders; Neutrophils; Risk Factors; Thrombopoiesis; Thrombosis
PubMed: 26869607
DOI: 10.1093/eurheartj/ehv718 -
Cancers Jun 2023Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent... (Review)
Review
Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings. Individuals with constitutional trisomy 21 have a profound dosage imbalance in the hematopoiesis-governing genes located on chromosome 21 and thus are subject to impaired fetal as well as to neonatal erythro-megakaryopoiesis. Almost all neonates with DS develop quantitative and morphological hematological abnormalities, yet still only 5-10% of them present with one of the preleukemic or leukemic conditions of DS. The acquired mutations in the key hematopoietic transcription factor gene , found solely in cells trisomic for chromosome 21, are considered to be the essential step for the selective growth advantage of leukemic cells. While the majority of cases of TAM remain clinically 'silent' or undergo spontaneous remission, the remaining 20% to 30% of them progress into ML-DS until the age of 4 years. The hypersensitivity of ML-DS blasts to chemotherapeutic agents, including but not limited to cytarabine, and drugs' increased infectious and cardiac toxicity have necessitated the development of risk-adapted treatment protocols for children with ML-DS. Recent advances in cytogenetics and specific molecular mechanisms involved in the evolution of TAM and ML-DS are reviewed here, as well as their integration in the improvement of risk stratification and targeted management of ML-DS.
PubMed: 37444375
DOI: 10.3390/cancers15133265 -
Molecular Aspects of Medicine Feb 2021Hematopoietic stem cells (HSC) lie at the center of the hematopoiesis process, as they bear capacity to self-renew and generate all hematopoietic lineages, hence, all... (Review)
Review
Hematopoietic stem cells (HSC) lie at the center of the hematopoiesis process, as they bear capacity to self-renew and generate all hematopoietic lineages, hence, all mature blood cells. The ability of HSCs to recognize systemic infection or inflammation or other forms of peripheral stress, such as blood loss, is essential for demand-adapted hematopoiesis. Also of critical importance for HSC function, specific metabolic cues (e.g., associated with changes in energy or O levels) can regulate HSC function and fate decisions. In this regard, the metabolic adaptation of HSCs facilitates their switching between different states, namely quiescence, self-renewal, proliferation and differentiation. Specific metabolic alterations in hematopoietic stem and progenitor cells (HSPCs) have been linked with the induction of trained myelopoiesis in the bone marrow as well as with HSPC dysfunction in aging and clonal hematopoiesis of indeterminate potential (CHIP). Thus, HSPC function is regulated by both immunologic/inflammatory and metabolic cues. The immunometabolic control of HSPCs and of hematopoiesis is discussed in this review along with the translational implications thereof, that is, how metabolic pathways can be therapeutically manipulated to prevent or reverse HSPC dysfunction or to enhance or attenuate trained myelopoiesis according to the needs of the host.
Topics: Cell Differentiation; Cell Proliferation; Hematopoiesis; Hematopoietic Stem Cells; Humans; Inflammation
PubMed: 33160640
DOI: 10.1016/j.mam.2020.100923 -
Current Opinion in Lipidology Oct 2019Monocytes and macrophages are key players in the pathogenesis of atherosclerosis and dictate atherogenesis growth and stability. The heterogeneous nature of myeloid... (Review)
Review
PURPOSE OF REVIEW
Monocytes and macrophages are key players in the pathogenesis of atherosclerosis and dictate atherogenesis growth and stability. The heterogeneous nature of myeloid cells concerning their metabolic and phenotypic function is increasingly appreciated. This review summarizes the recent monocyte and macrophage literature and highlights how differing subsets contribute to atherogenesis.
RECENT FINDINGS
Monocytes are short-lived cells generated in the bone marrow and released to circulation where they can produce inflammatory cytokines and, importantly, differentiate into long-lived macrophages. In the context of cardiovascular disease, a myriad of subtypes, exist with each differentially contributing to plaque development. Herein we describe recent novel characterizations of monocyte and macrophage subtypes and summarize the recent literature on mediators of myelopoiesis.
SUMMARY
An increased understanding of monocyte and macrophage phenotype and their molecular regulators is likely to translate to the development of new therapeutic targets to either stem the growth of existing plaques or promote plaque stabilization.
Topics: Atherosclerosis; Bone Marrow Cells; Cell Differentiation; Cytokines; Humans; Macrophages; Monocytes; Myelopoiesis; Plaque, Atherosclerotic
PubMed: 31361625
DOI: 10.1097/MOL.0000000000000634 -
Nature Reviews. Immunology Mar 2020Genetic defects that accumulate in haematopoietic stem cells (HSCs) are thought to be responsible for age-related changes in haematopoiesis that include a decline in... (Review)
Review
Genetic defects that accumulate in haematopoietic stem cells (HSCs) are thought to be responsible for age-related changes in haematopoiesis that include a decline in lymphopoiesis and skewing towards the myeloid lineage. This HSC-centric view is based largely on studies showing that HSCs from aged mice exhibit these lineage biases following transplantation into irradiated young recipient mice. In this Opinion article, we make the case that the reliance on this approach has led to inaccurate conclusions regarding the effects of ageing on blood-forming stem cells; we suggest instead that changes in the environment contribute to haematopoietic system ageing. We propose that a complete understanding of how ageing affects haematopoiesis depends on the analysis of blood cell production in unperturbed mice. We describe how this can be achieved using in situ fate mapping. This approach indicates that changes in downstream progenitors, in addition to any HSC defects, may explain the reduced lymphopoiesis and sustained myelopoiesis that occur during ageing.
Topics: Aging; Animals; Cell Differentiation; Cell Lineage; Cellular Senescence; Hematopoiesis; Hematopoietic Stem Cells; Humans; Myelopoiesis
PubMed: 31740804
DOI: 10.1038/s41577-019-0236-2 -
Immunity Feb 2019Myelopoiesis ensures the steady state of the myeloid cell compartment. Technological advances in fate mapping and genetic engineering, as well as the advent of single... (Review)
Review
Myelopoiesis ensures the steady state of the myeloid cell compartment. Technological advances in fate mapping and genetic engineering, as well as the advent of single cell RNA-sequencing, have highlighted the heterogeneity of the hematopoietic system and revealed new concepts in myeloid cell ontogeny. These technologies are also shedding light on mechanisms of myelopoiesis at homeostasis and at different phases of infection and inflammation, illustrating important feedback loops between affected tissues and the bone marrow. We review these findings here and revisit principles in myelopoiesis in light of the evolving understanding of myeloid cell ontogeny and heterogeneity. We argue for the importance of system-wide evaluation of changes in myelopoiesis and discuss how even after the resolution of inflammation, long-lasting alterations in myelopoiesis may play a role in innate immune memory or trained immunity.
Topics: Animals; Bone Marrow; Homeostasis; Humans; Immunity, Innate; Infections; Inflammation; Models, Immunological; Myeloid Cells; Myeloid Progenitor Cells; Myelopoiesis
PubMed: 30784577
DOI: 10.1016/j.immuni.2019.01.019 -
Cell Regeneration (London, England) Jan 2023Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and... (Review)
Review
Myelopoiesis is the process in which the mature myeloid cells, including monocytes/macrophages and granulocytes, are developed. Irregular myelopoiesis may cause and deteriorate a variety of hematopoietic malignancies such as leukemia. Myeloid cells and their precursors are difficult to capture in circulation, let alone observe them in real time. For decades, researchers had to face these difficulties, particularly in in-vivo studies. As a unique animal model, zebrafish possesses numerous advantages like body transparency and convenient genetic manipulation, which is very suitable in myelopoiesis research. Here we review current knowledge on the origin and regulation of myeloid development and how zebrafish models were applied in these studies.
PubMed: 36595106
DOI: 10.1186/s13619-022-00139-2 -
Trends in Molecular Medicine May 2019In contrast to traditional immune cell-centered viewpoints, recent studies suggest that tissues are not passive recipients of immunity but have a 'regulatory say' over... (Review)
Review
In contrast to traditional immune cell-centered viewpoints, recent studies suggest that tissues are not passive recipients of immunity but have a 'regulatory say' over the host inflammatory response. Identification of tissue-derived homeostatic molecules regulating immune plasticity is seminal for understanding the inherent regulatory potential of different organs in the immune response. DEL-1 (developmental endothelial locus-1) is a secreted multidomain protein interacting with integrins and phospholipids and regulates, depending on its expression location, distinct stages of the host inflammatory response (from myelopoiesis over leukocyte recruitment to efferocytosis and resolution of inflammation). Here we synthesize recent evidence of DEL-1 as an exemplar local regulatory factor in the context of tissue immune plasticity and inflammatory disorders (such as periodontitis, multiple sclerosis, and pulmonary disorders), and discuss its potential as a therapeutic agent.
Topics: Animals; Calcium-Binding Proteins; Cell Adhesion Molecules; Cell Plasticity; Chemotaxis, Leukocyte; Disease Susceptibility; Homeostasis; Humans; Immunomodulation; Inflammation; Myelopoiesis; Neutrophils; Organ Specificity; Phagocytosis; Protein Binding; Signal Transduction; Structure-Activity Relationship
PubMed: 30885428
DOI: 10.1016/j.molmed.2019.02.010 -
Journal of Leukocyte Biology Nov 2016The gut microbiota is a complex and dynamic microbial ecosystem that plays a fundamental role in host physiology. Locally, the gut commensal microbes/host symbiotic... (Review)
Review
The gut microbiota is a complex and dynamic microbial ecosystem that plays a fundamental role in host physiology. Locally, the gut commensal microbes/host symbiotic relationship is vital for barrier fortification, nutrient absorption, resistance against intestinal pathogens, and the development and maintenance of the mucosal immune system. It is now clear that the effects of the indigenous intestinal flora extend beyond the gut, ranging from shaping systemic immune responses to metabolic and behavioral functions. However, the underlying mechanisms of the gut microbiota/systemic immune system interactions remain largely unknown. Myeloid cells respond to microbial signals, including those derived from commensals, and initiate innate and adaptive immune responses. In this review, we focus on the impact of the gut microbiota on myeloid cells at extraintestinal sites. In particular, we discuss how commensal-derived signals affect steady-state myelopoiesis and cellular function and how that influences the response to infection and cancer therapy.
Topics: Adaptive Immunity; Animals; Cytokines; Dysbiosis; Gastrointestinal Microbiome; Homeostasis; Humans; Immunity, Innate; Infections; Inflammation; Models, Immunological; Myeloid Cells; Myelopoiesis; Neoplasms; Neutrophils; Symbiosis; Vaccine Potency
PubMed: 27605211
DOI: 10.1189/jlb.3RI0516-222R