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Red bone marrow hosts metabolically active enucleated adipocytes that support hematopoiesis

ABSTRACT: Bone marrow adipocytes (BMAds) are a major component of the bone marrow (BM) that regulates bone turnover and hematopoiesis. In rodents, two distinct adipocyte populations exist: constitutive BMAds (cBMAds), located in areas devoid of hematopoietic cells and resistant to metabolic cues, and regulatory BMAds (rBMAds), interspersed within hematopoietic niches and responsive to energy stress. Despite their potential importance, rBMAds have remained poorly characterized due to their scarcity in rodents. Here, we used a high-yield method to isolate human rBMAds, enabling structural, proteomic, lipidomic, and functional analyses. Remarkably, human rBMAds are anucleate yet retain organelles and sustain lipid and glucose metabolic pathways but, unlike rodent rBMAds, display no lipolytic activity. They actively secrete factors that support hematopoiesis in vitro, implicating them as functional contributors to the BM niche. These findings suggest that human rBMAds may arise from cBMAds through terminal differentiation and define a novel adipocyte subtype critical for BM homeostasis.

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ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Emmanuelle Mouton Barbosa

LAB HEAD: Odile Burlet-Schiltz

PROVIDER: PXD071439 | Pride | 2026-06-01

REPOSITORIES: Pride

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Project description:Native bone marrow mesenchymal stem/stromal cells (BM-MSCs) participate in generating and shaping the skeleton and bone marrow 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 per se 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. 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 bioinformatics analyses at different levels to identify, characterize and classify distinct native subsets with relevant biomarkers. 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 to reveal 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. 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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	F147820.dat	Other
	F147821.dat	Other
	F147822.dat	Other
	F147823.dat	Other
	F147824.dat	Other

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Red bone marrow hosts metabolically active enucleated adipocytes that support hematopoiesis

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