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Current Opinion in Hematology Jan 2021The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of... (Review)
Review
PURPOSE OF REVIEW
The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of hematopoietic stem cells (HSC), multipotent progenitors (MPP), and lineage committed progenitors to produce the large number of blood cells required to sustain life. The bone marrow is notoriously difficult to image; because of this the anatomy of blood cell production -- and how local signals spatially organize hematopoiesis -- are not well defined. Here we review our current understanding of the spatial organization of the mouse bone marrow with a special focus in recent advances that are transforming our understanding of this tissue.
RECENT FINDINGS
Imaging studies of HSC and their interaction with candidate niches have relied on ex-vivo imaging of fixed tissue. Two recent manuscripts demonstrating live imaging of subsets of HSC in unperturbed bone marrow have revealed unexpected HSC behavior and open the door to examine HSC regulation, in situ, over time. We also discuss recent findings showing that the bone marrow contains distinct microenvironments, spatially organized, that regulate unique aspects of hematopoiesis.
SUMMARY
Defining the spatial architecture of hematopoiesis in the bone marrow is indispensable to understand how this tissue ensures stepwise, balanced, differentiation to meet organism demand; for deciphering alterations to hematopoiesis during disease; and for designing organ systems for blood cell production ex vivo.
Topics: Animals; Bone Marrow; Hematopoiesis; Hematopoietic Stem Cells; Humans; Stem Cell Niche
PubMed: 33177411
DOI: 10.1097/MOH.0000000000000621 -
Nature Jan 2014Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches,... (Review)
Review
Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
Topics: Animals; Bone Marrow; Bone and Bones; Endothelial Cells; Hematopoietic Stem Cells; Humans; Mesenchymal Stem Cells; Osteoblasts; Stem Cell Niche
PubMed: 24429631
DOI: 10.1038/nature12984 -
Cancer Reports (Hoboken, N.J.) Apr 2019Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a... (Review)
Review
BACKGROUND
Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts.
RECENT FINDINGS
In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis.
CONCLUSION
Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.
Topics: Animals; Bone Marrow; Hematopoiesis; Humans; Leukemia; Metabolic Networks and Pathways; Stem Cell Niche; Tumor Microenvironment
PubMed: 32721091
DOI: 10.1002/cnr2.1139 -
Nature Neuroscience May 2022It remains unclear how immune cells from skull bone marrow niches are recruited to the meninges. Here we report that cerebrospinal fluid (CSF) accesses skull bone marrow...
It remains unclear how immune cells from skull bone marrow niches are recruited to the meninges. Here we report that cerebrospinal fluid (CSF) accesses skull bone marrow via dura-skull channels, and CSF proteins signal onto diverse cell types within the niches. After spinal cord injury, CSF-borne cues promote myelopoiesis and egress of myeloid cells into meninges. This reveals a mechanism of CNS-to-bone-marrow communication via CSF that regulates CNS immune responses.
Topics: Bone Marrow; Cerebrospinal Fluid; Head; Meninges; Myeloid Cells; Skull
PubMed: 35301477
DOI: 10.1038/s41593-022-01029-1 -
Endocrine Reviews Oct 2019The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention... (Review)
Review
The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention from the research community. Advancements in mouse transgenics and imaging methods, particularly in the last 10 years, have permitted more detailed examinations of marrow adipocytes than ever before and yielded data that show these cells are critical regulators of the BM microenvironment and whole-body metabolism. Indeed, marrow adipocytes are anatomically and functionally separate from brown, beige, and classic white adipocytes. Thus, areas of BM space populated by adipocytes can be considered distinct fat depots and are collectively referred to as marrow adipose tissue (MAT) in this review. In the proceeding text, we focus on the developmental origin and physiologic functions of MAT. We also discuss the signals that cause the accumulation and loss of marrow adipocytes and the ability of these cells to regulate other cell lineages in the BM. Last, we consider roles for MAT in human physiology and disease.
Topics: Adipocytes; Adiposity; Animals; Bone Marrow; Humans; Signal Transduction
PubMed: 31127816
DOI: 10.1210/er.2018-00138 -
Current Osteoporosis Reports Dec 2016This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility. (Review)
Review
PURPOSE OF REVIEW
This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility.
RECENT FINDINGS
Advances in non-invasive imaging have facilitated marrow fat research in humans. In contrast to animal studies which clearly demonstrate higher levels of marrow fat in diabetes, human studies have shown smaller and less certain differences. Marrow fat has been reported to correlate with A1c, and there may be a distinct marrow lipid saturation profile in diabetes. Greater marrow fat is associated with impaired skeletal health. Marrow fat may be a mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone alterations, visceral adiposity, and hypoleptinemia have been associated with greater marrow fat and may represent potential mechanisms for the putative effects of diabetes on marrow fat, although other factors likely contribute. Additional research is needed to further define the role of marrow fat in diabetic skeletal fragility and to determine whether marrow fat is a therapeutic target.
Topics: Adipose Tissue; Adiposity; Animals; Bone Density; Bone Marrow; Diabetes Mellitus; Humans; Magnetic Resonance Imaging; Osteoblasts; Osteoporosis; Proton Magnetic Resonance Spectroscopy
PubMed: 27714580
DOI: 10.1007/s11914-016-0336-x -
Nature Reviews. Endocrinology Nov 2023Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis,... (Review)
Review
Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered.
Topics: Humans; Adipocytes; Adipose Tissue; Bone Marrow; Bone Marrow Cells; Obesity; Weight Loss
PubMed: 37587198
DOI: 10.1038/s41574-023-00879-4 -
Frontiers in Immunology 2021The shape and spatial organization -the anatomy- of a tissue profoundly influences its function. Knowledge of the anatomical relationships between parent and daughter... (Review)
Review
The shape and spatial organization -the anatomy- of a tissue profoundly influences its function. Knowledge of the anatomical relationships between parent and daughter cells is necessary to understand differentiation and how the crosstalk between the different cells in the tissue leads to physiological maintenance and pathological perturbations. Blood cell production takes place in the bone marrow through the progressive differentiation of stem cells and progenitors. These are maintained and regulated by a heterogeneous microenvironment composed of stromal and hematopoietic cells. While hematopoiesis has been studied in extraordinary detail through functional and multiomics approaches, much less is known about the spatial organization of blood production and how local cues from the microenvironment influence this anatomy. Here, we discuss some of the studies that revealed a complex anatomy of hematopoiesis where discrete local microenvironments spatially organize and regulate specific subsets of hematopoietic stem cells and/or progenitors. We focus on the open questions in the field and discuss how new tools and technological advances are poised to transform our understanding of the anatomy of hematopoiesis.
Topics: Animals; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Cellular Microenvironment; Hematopoiesis; Hematopoietic Stem Cells; Humans; Models, Biological; Stem Cell Niche
PubMed: 34858426
DOI: 10.3389/fimmu.2021.768439 -
Frontiers in Immunology 2020Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise... (Review)
Review
Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.
Topics: Animals; Bone Marrow; Cellular Microenvironment; Hematopoiesis; Humans; Infections
PubMed: 33324404
DOI: 10.3389/fimmu.2020.585402 -
International Journal of Molecular... Feb 2021Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis... (Review)
Review
Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.
Topics: Bone Marrow; Cell Communication; Exosomes; Humans; Leukemia; Tumor Microenvironment
PubMed: 33668652
DOI: 10.3390/ijms22041881