Human Bone Marrow Adipose Tissue is a Hematopoietic Niche for Leptin-DrivenMonopoiesis

Loureiro, Z. Y., Samant, A., Desai, A., DeSouza, T., Cirka, H., Ceesay, M., Kostyra, D., Joyce, S., Khair, L., Solivan-Rivera, J., Ziegler, R., Ketelut Carneiro, N., Tsai, L. A., Brehm, M., Messina, L. M., Fitzgerald, K. A., Rosen, E., Corvera, S., Nguyen, T. T.

Diabetes Center of Excellence, Morningside Graduate School of Biomedical Sciences, Program in Molecular Medicine, University of Massachusetts Chan Medical Schoo · biorxiv

Paper

Abstract

During aging, adipose tissue within the bone marrow expands while the trabecular red marrow contracts. The impact of these changes on blood cell formation remains unclear. To address this question, we performed single-cell and single-nuclei transcriptomic analysis on adipose-rich yellow bone marrow (BMY) and adipose-poor trabecular red marrow (BMR) from human subjects undergoing lower limb amputations. Surprisingly, we discovered two distinct hematopoietic niches, in which BMY contains a higher number of monocytes and progenitor cells expressing genes associated with inflammation. To further investigate these niches, we developed an in-vitro organoid system that maintains features of the human bone marrow. We find cells from BMY are distinct in their expression of the leptin receptor, and respond to leptin stimulation with enhanced proliferation, leading to increased monocyte production. These findings suggest that the age-associated expansion of bone marrow adipose tissue drives a pro-inflammatory state by stimulating monocyte production from a spatially distinct, leptin-responsive hematopoietic stem/progenitor cell population.

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Research summary

The paper claims that the expansion of bone marrow adipose tissue drives a pro-inflammatory state by stimulating monocyte production from a distinct hematopoietic stem/progenitor cell population. This research is relevant as it explores the relationship between aging, bone marrow changes, and inflammation, which are critical factors in understanding the mechanisms of aging and potential interventions.

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