Spatial and biochemical interactions between bone marrow adipose tissue and hematopoietic stem and progenitor cells in rhesus macaques

Robino, Jacob J; Pamir, Nathalie; Rosário, Sara; Crawford, Lindsey B.; Burwitz, Benjamin J.; Roberts, Charles T.; Kurre, Peter; Varlamov, Oleg

doi:10.1016/j.bone.2020.115248

Cited by 14 publications

(23 citation statements)

References 84 publications

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“…The red marrow of the control femurs was sub-compartmentalized into small pockets formed by ossified trabeculae. In contrast, the red marrow of WSD femurs was localized to the BM cavity in close proximity to BM adipocytes ( Figure 1G, arrow ), which resembles the structural organization of the femurs in juvenile and adult rhesus macaques (Robino et al, 2020). Collectively, our anthropometric and histological analyses demonstrate that maternal weight during pregnancy positively correlates with fetal growth and induces premature FBM adipogenesis and a postnatal pattern of bone development ( Supplementary Figure 1A ).…”

Section: Resultsmentioning

confidence: 87%

“…Heightened inflammatory responses by BM stromal macrophages could modulate the development of myeloid progenitors leading to "immune-tolerant phenotype" in mature monocytes. Recent studies from our and other laboratories have shown that BM adipocytes may potentiate myeloid-biased differentiation of HSPCs in adult rhesus macaques (Robino et al, 2020) was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Discussionmentioning

confidence: 99%

“…RBC-free cell pellets were processed and cryopreserved in 4-5 aliquots as described (Robino et al, 2020; Varlamov et al, 2020). Cryopreserved cells, including tibial FBM and PBMCs, were analyzed by flow cytometry using monoclonal antibodies validated for binding to rhesus macaque proteins (Burwitz et al, 2014) and lymphoid-specific and myeloid-specific gating strategies.…”

Section: Methodsmentioning

confidence: 99%

“…FBM mononuclear cells were isolated by centrifugation for 30 minutes at room temperature on a Ficoll gradient (StemCell Technologies, Vancouver, BC, Canada) and red blood cells were removed using the RBC lysis buffer (StemCell Technologies). Mononuclear cells were washed three times with PBS and CD34+ cells were isolated as described (Robino et al, 2020) using rhesus macaque-specific antibodies to CD34 (clone 563; BD Pharmingen, San Jose, CA, USA) and the anti-PE MACS magnetic bead system (Miltenyi Biotec, Bergisch Gladbach, Germany) with the supplied reagents. CD34+ HSPC and CD34-flow-through cell fractions were cryopreserved in several aliquots using CryoStor CS10 (Stem Cells Technologies).…”

Section: Cell Isolationmentioning

confidence: 99%

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Maternal Western-Style Diet Impairs Bone Marrow Development and Drives a Hyperinflammatory Phenotype in Hematopoietic Stem and Progenitor Cells in Fetal Rhesus Macaques

Sureshchandra

Jj²,

Goldman

et al. 2021

Preprint

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Infants from obese moms have an increased susceptibility to immune dysregulation. However, the mechanisms by which maternal obesity alters fetal hematopoiesis remain largely unknown. Here, we determined the impact of maternal consumption of an obesogenic western-style diet (WSD) on hematopoietic development in fetal rhesus macaques using a combination of phenotypic, functional, and genomic assays. We demonstrate that maternal WSDresulted in accelerated fetal growth and altered fetal hematopoiesis. Specifically, single-cell RNA sequencing analysis of fetal bone marrow HSPCs showed that maternal WSD altered the transcriptional program of the common lymphoid progenitors and decreased the frequencies of bone marrow B-cells and NK-cells. Despite an expansion of monocyte progenitors in FBM, fetal blood monocytes from the WSD group demonstrated a blunted response to bacterial lipopolysaccharide. Furthermore, maternal WSD led to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2 γ-/-mice. Collectively, this study demonstrates that maternal WSD dysregulates fetal HSPC development.

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Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Cell Isolationmentioning

confidence: 99%

See 2 more Smart Citations

Maternal Western-Style Diet Impairs Bone Marrow Development and Drives a Hyperinflammatory Phenotype in Hematopoietic Stem and Progenitor Cells in Fetal Rhesus Macaques

Sureshchandra

Jj²,

Goldman

et al. 2021

Preprint

Self Cite

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“…In contrast, cellularity was not reduced in the sternums of 24month-old C57BL/6 mice. Adipocytes have been linked to increased myeloid bias in mice [15], rhesus monkeys [31], and humans [1,15]. However, the presence of only rare adipocytes in the mouse sternums and in the mouse femoral heads with aging [32] may indicate differences in the regulation of steady-state myelopoiesis [33].…”

Section: Discussionmentioning

confidence: 99%

Human, mouse, and dog bone marrow show similar mesenchymal stromal cells within a distinctive microenvironment

Meza-León

Gratzinger

Aguilar-Navarro

et al. 2021

Experimental Hematology

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Bone marrow stromal cells (BMSCs) are a key part of the hematopoietic niche. Mouse and human BMSCs are recognized by different markers (LepR and NGFR/CD271, respectively). However, there has not been a detailed in situ comparison of both populations within the hematopoietic microenvironment. Moreover, dog BMSCs have not been characterized in situ by any of those markers. We conducted a systematic histopathological comparison of mouse, human, and dog BMSCs within their bone marrow architecture and microenvironment. Human and dog CD271+ BMSCs had a morphology, frequency, and distribution within trabecular bone marrow similar to those of mouse LepR+ BMSCs. However, mouse bone marrow had higher cellularity and megakaryocyte content. In conclusion, highly comparable bone marrow mesenchymal stromal cell distribution among the three species establishes the validity of using mouse and dog as a surrogate experimental model of hematopoietic stem cell−BMSC interactions. However, the distinct differences in adipocyte and megakaryocyte microenvironment content of mouse bone marrow and how they might influence hematopoietic stem cell interactions as compared with humans require further study.

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Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging

et al. 2022

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Extracellular vesicles (EVs), including exosomes and microvesicles, are released by numerous cell types. EVs are now acknowledged as playing a critical role in cell-cell communication in healthy aging as well as in age-related diseases. Recently it was shown that senescence, a key hallmark of aging, increases the secretion of EVs. Moreover, EVs can transport proteins and microRNAs (miRNAs) that are key components of the senescence-associated secretory phenotype (SASP). Here we review evidence that SASP-related miRNAs are involved in musculoskeletal degeneration with aging. Specifically, senescence-related miRNAs are elevated in EVs released by skeletal muscle myocytes and fibro-adipogenic progenitor cells with aging and disuse atrophy, respectively. Many of these same senescence-related miRNAs are detected in EVs from the synovial fluid of patients with osteoarthritis, and these miRNAs can contribute to cartilage degeneration. Finally, senescence-associated miRNAs are secreted from bone marrow-derived stem (stromal) cells impacting neighboring hematopoietic stem cells and circulating in the blood. The senescence-associated miRNA mir-34a, which is known to target Wnt and Notch pathways as well as the cell survival factors Sirt1 and Bcl2, is detected in EVs from human and animal subjects with muscle atrophy, bone loss, and osteoarthritis. These findings suggest that suppressing the secretion of EV-derived, senescence-related miRNAs, such as miR-34a, or increasing levels of competing endogenous long noncoding RNAs, such as MALAT1 that inhibit miR-34a, may help to improve musculoskeletal function with aging.

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Spatial and biochemical interactions between bone marrow adipose tissue and hematopoietic stem and progenitor cells in rhesus macaques

Cited by 14 publications

References 84 publications

Maternal Western-Style Diet Impairs Bone Marrow Development and Drives a Hyperinflammatory Phenotype in Hematopoietic Stem and Progenitor Cells in Fetal Rhesus Macaques

Maternal Western-Style Diet Impairs Bone Marrow Development and Drives a Hyperinflammatory Phenotype in Hematopoietic Stem and Progenitor Cells in Fetal Rhesus Macaques

Human, mouse, and dog bone marrow show similar mesenchymal stromal cells within a distinctive microenvironment

Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging

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