Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow

Ludin, Aya; Itkin, Tomer; Gur-Cohen, Shiri; Mildner, Alexander; Shezen, Elias; Golan, Karin; Kollet, Orit; Kalinkovich, Alexander; Porat, Ziv; D’Uva, Gabriele; Schajnovitz, Amir; Voronov, Elena; Brenner, David A.; Apte, Ron N.; Jung, Steffen; Lapidot, Tsvee

doi:10.1038/ni.2408

Cited by 188 publications

(151 citation statements)

References 47 publications

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“…93 PGE2 rapidly increases in the marrow microenvironment after radiation, and treatment of mice with dimethyl-PGE2 after sublethal radiation injury suppresses apoptotic gene expression in HSPCs and stimulates cyclooxygenase-2 activity in the marrow, specifically in a population of a-smooth muscle actin 1 macrophages that participate in HSC support. 94,95 Moreover, the PGE2 receptor EP4 (PGE receptor 4) regulates trafficking of HSCs in the bone marrow through modulation of mesenchymal/osteolineage populations. 96 These functions of PGE2 are operative in nonhuman primates and healthy volunteers, 96,97 providing a rationale for the use of drugs that modulate PGE2 expression to regulate HSPC function in the clinical setting.…”

Section: Prostaglandin E2mentioning

confidence: 99%

The hematopoietic stem cell niche in homeostasis and disease

Calvi

Link

2015

Blood

187

151

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The bone marrow microenvironment contains a heterogeneous population of stromal cells organized into niches that support hematopoietic stem cells (HSCs) and other lineage-committed hematopoietic progenitors. The stem cell niche generates signals that regulate HSC self-renewal, quiescence, and differentiation. Here, we review recent studies that highlight the heterogeneity of the stromal cells that comprise stem cell niches and the complexity of the signals that they generate. We highlight emerging data that stem cell niches in the bone marrow are not static but instead are responsive to environmental stimuli. Finally, we review recent data showing that hematopoietic niches are altered in certain hematopoietic malignancies, and we discuss how these alterations might contribute to disease pathogenesis.

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Section: Prostaglandin E2mentioning

confidence: 99%

The hematopoietic stem cell niche in homeostasis and disease

Calvi

Link

2015

Blood

187

151

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“…Finally, a direct contact between HSPCs and macrophages has also been observed that seems to preserve HSC function under stress [108]. It is unknown whether emerging HSCs are also influenced by hematopoietic progenitors that are already present at that point in development.…”

Section: Other Hematopoietic Cellsmentioning

confidence: 99%

Concise Review: From Greenhouse to Garden: The Changing Soil of the Hematopoietic Stem Cell Microenvironment During Development

2014

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The hematopoietic system has been intensely studied for many decades. For this reason, it has become the best understood stem cell-derived system that serves as a paradigm for stem cell biology and has found numerous applications in the clinics. While a lot of progress has recently been made in describing the bone marrow components that maintain and control blood stem cell function in the adult, very little is currently known about the regulatory microenvironment in which the first adult-repopulating hematopoietic stem cells are formed during development. Knowledge of these processes is crucial for understanding the basic regulation of hematopoietic stem cell production and behavior and to allow their in vitro expansion and generation from embryonic stem cells or iPS cells for clinical and research purposes. This review summarizes the recent advances that have been made in defining the cellular components, as well as the soluble and physical factors, that are part of the niche involved in regulating hematopoietic stem cell generation in the embryo. The findings are compared with what is known about the adult bone marrow niche to find common pathways for stem cell regulation, but also to highlight processes uniquely required for de novo hematopoietic stem cell generation, as these are the conditions that will need to be recreated for the successful production of blood stem cells in culture.

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“…Recently, a subset of monocytic/macrophage cells expressing the a-smooth muscle actin has been shown to promote the expression of Cxcl12 in perivascular Nestin? cells through the production of prostaglandin E2 [44]. In addition, activated macrophages can produce catecholamines [45], which have been shown to exert potent modulatory functions on Nestin?…”

Section: Bone Marrow Macrophagesmentioning

confidence: 99%

Innate immune cells as homeostatic regulators of the hematopoietic niche

et al. 2014

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Two cellular systems of paramount importance for mammalian physiology, the myeloid and the hematopoietic, have received a great deal of attention in the past decade. Myeloid leukocytes, classically involved in mediating innate immune responses, are now known to regulate other important aspects of the organism's physiology, from development to regulation of metabolic functions. In parallel, many diverse cellular and molecular components have been identified in the bone marrow (BM) that are required for the regulation and lifelong preservation of hematopoietic stem and progenitor cells (HSPC). Since the production of blood and immune elements by these multipotent cells responds to environmental signals, it is not entirely surprising that the hematopoietic niches in which HSPC are located can in turn be regulated by the immune system. We review here recent evidence demonstrating that two components of the innate immune system, macrophages and neutrophils, regulate the function of the hematopoietic niche in ways that may favor both the retention and the release of HSPC from the BM. We propose that the highly migratory nature of neutrophils, the presence of a network of tissue-resident macrophages in the BM and possibly in other tissues, and the superb capacity of these innate immune cells to respond to stress endow them with regulatory functions that are ultimately relayed to the hematopoietic niche.

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Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow

Cited by 188 publications

References 47 publications

The hematopoietic stem cell niche in homeostasis and disease

The hematopoietic stem cell niche in homeostasis and disease

Concise Review: From Greenhouse to Garden: The Changing Soil of the Hematopoietic Stem Cell Microenvironment During Development

Innate immune cells as homeostatic regulators of the hematopoietic niche

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