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

Meza-León, Berenice; Gratzinger, Dita; Aguilar-Navarro, Alicia G.; Juárez-Aguilar, Fany G.; Rebel, Vivienne I.; Torlakovic, Emina; Purton, Louise E.; Dorantes-Acosta, Elisa; Escobar-Sánchez, Argelia; Dick, John E.; Flores-Figueroa, Eugenia

doi:10.1016/j.exphem.2021.06.006

Cited by 5 publications

(3 citation statements)

References 42 publications

(38 reference statements)

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“…However, histological analysis of the bone marrow of our mice revealed no obvious differences in the proportion of fat cells or signs of fibrosis in the mutant animals. As previously described for bone marrow in the sternum of mice, fat cells were almost absent 41 . Therefore, increased cellularity of the bone marrow with reduced interstitial fluid and vascularization could be the cause of the decreased T1 relaxation times in the mutants.…”

Section: Discussionmentioning

confidence: 63%

Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI

Kraiger

Klein-Rodewald

Rathkolb

et al. 2022

Sci Rep

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Animal models are an indispensable platform used in various research disciplines, enabling, for example, studies of basic biological mechanisms, pathological processes and new therapeutic interventions. In this study, we applied magnetic resonance imaging (MRI) to characterize the clinical picture of a novel N-ethyl-N-nitrosourea-induced Kit-mutant mouse in vivo. Seven C3H KitN824K/WT mutant animals each of both sexes and their littermates were monitored every other month for a period of twelve months. MRI relaxometry data of hematopoietic bone marrow and splenic tissue as well as high-resolution images of the gastrointestinal organs were acquired. Compared with controls, the mutants showed a dynamic change in the shape and volume of the cecum and enlarged Peyer´s patches were identified throughout the entire study. Mammary tumors were observed in the majority of mutant females and were first detected at eight months of age. Using relaxation measurements, a substantial decrease in longitudinal relaxation times in hematopoietic tissue was detected in mutants at one year of age. In contrast, transverse relaxation time of splenic tissue showed no differences between genotypes, except in two mutant mice, one of which had leukemia and the other hemangioma. In this study, in vivo MRI was used for the first time to thoroughly characterize the evolution of systemic manifestations of a novel Kit-induced tumor model and to document the observable organ-specific disease cascade.

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Section: Discussionmentioning

confidence: 63%

Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI

Kraiger

Klein-Rodewald

Rathkolb

et al. 2022

Sci Rep

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“…We found MARCKS highly expressed in native BM-MSCs, and immuno-histology staining showed strong expression in phenotypically reticular cells that could be associated with MSCs in accordance with the similar labeling by LEPR antibodies. This feature was also seen when BM was stained for CD271 expression, a well-known native MSC marker [ 69 ]. MARCKS + cells are located from the abluminal position of vessels to trabecular bone.…”

Section: Discussionmentioning

confidence: 97%

Single-cell RNA sequencing of human non-hematopoietic bone marrow cells reveals a unique set of inter-species conserved biomarkers for native mesenchymal stromal cells

Fiévet,

Espagnolle,

Gerovska

et al. 2023

Stem Cell Res Ther

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Background Native bone marrow (BM) mesenchymal stem/stromal cells (BM-MSCs) participate in generating and shaping the skeleton and BM throughout the lifespan. Moreover, BM-MSCs regulate hematopoiesis by contributing to the hematopoietic stem cell niche in providing critical cytokines, chemokines and extracellular matrix components. However, BM-MSCs contain a heterogeneous cell population that remains ill-defined. Although studies on the taxonomy of native BM-MSCs in mice have just started to emerge, the taxonomy of native human BM-MSCs remains unelucidated. Methods By using single-cell RNA sequencing (scRNA-seq), we aimed to define a proper taxonomy for native human BM non-hematopoietic subsets including endothelial cells (ECs) and mural cells (MCs) but with a focal point on MSCs. To this end, transcriptomic scRNA-seq data were generated from 5 distinct BM donors and were analyzed together with other transcriptomic data and with computational biology analyses at different levels to identify, characterize and classify distinct native cell subsets with relevant biomarkers. Results We could ascribe novel specific biomarkers to ECs, MCs and MSCs. Unlike ECs and MCs, MSCs exhibited an adipogenic transcriptomic pattern while co-expressing genes related to hematopoiesis support and multilineage commitment potential. Furthermore, by a comparative analysis of scRNA-seq of BM cells from humans and mice, we identified core genes conserved in both species. Notably, we identified MARCKS, CXCL12, PDGFRA, and LEPR together with adipogenic factors as archetypal biomarkers of native MSCs within BM. In addition, our data suggest some complex gene nodes regulating critical biological functions of native BM-MSCs together with a preferential commitment toward an adipocyte lineage. Conclusions Overall, our taxonomy for native BM non-hematopoietic compartment provides an explicit depiction of gene expression in human ECs, MCs and MSCs at single-cell resolution. This analysis helps enhance our understanding of the phenotype and the complexity of biological functions of native human BM-MSCs.

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“…Multiple studies have demonstrated the existence of distinct subsets of MSCs, which express CD271 and/or CD146 and exhibit periendosteal or perivascular (arterial or sinusoidal) locations in human BM. 128 , 129 , 130 As in mice, when cultured in vitro, these cells exhibit trilineage differentiation. 129 Recent work identified a subset of CD271 + cells, which shares a high degree of homology with murine CARc, based principally on the prominent expression of Cxcl12 and Scf , as well as key CARc‐specific transcription factors such as Ebf3 and Foxc1 .…”

Section: Hsc Niches In Human Bmmentioning

confidence: 99%

Bone marrow niches for hematopoietic stem cells

Pereira,

Galli,

Nombela‐Arrieta

2024

HemaSphere

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Hematopoietic stem cells (HSCs) are the cornerstone of the hematopoietic system. HSCs sustain the continuous generation of mature blood derivatives while self‐renewing to preserve a relatively constant pool of progenitors throughout life. Yet, long‐term maintenance of functional HSCs exclusively takes place in association with their native tissue microenvironment of the bone marrow (BM). HSCs have been long proposed to reside in fixed and identifiable anatomical units found in the complex BM tissue landscape, which control their identity and fate in a deterministic manner. In the last decades, tremendous progress has been made in the dissection of the cellular and molecular fabric of the BM, the structural organization governing tissue function, and the plethora of interactions established by HSCs. Nonetheless, a holistic model of the mechanisms controlling HSC regulation in their niche is lacking to date. Here, we provide an overview of our current understanding of BM anatomy, HSC localization, and crosstalk within local cellular neighborhoods in murine and human tissues, and highlight fundamental open questions on how HSCs functionally integrate in the BM microenvironment.

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

Cited by 5 publications

References 42 publications

Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI

Monitoring longitudinal disease progression in a novel murine Kit tumor model using high-field MRI

Single-cell RNA sequencing of human non-hematopoietic bone marrow cells reveals a unique set of inter-species conserved biomarkers for native mesenchymal stromal cells

Bone marrow niches for hematopoietic stem cells

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