Abstract 4363142: Human Bone Marrow Adipose Tissue Functions as a Hematopoietic Niche for Leptin-Driven Monopoiesis

Tammy Nguyen; Zinger Yang Loureiro; Amruta Samant; Anand Desai; Tiffany DeSouza; Haley Cirka; Mai Ceesay; David Kostyra; Shannon Joyce; Lyne Khair; Javier Solivan-Rivera; Rachel Ziegler; Natalia Ketelut Carneiro; Linus Tsai; Brehm Michael; Katherine Fitzgerald; Evan Rosen; Silvia Corvera

doi:10.1161/circ.152.suppl_3.4363142

Abstract 4363142: Human Bone Marrow Adipose Tissue Functions as a Hematopoietic Niche for Leptin-Driven Monopoiesis

T Tammy Nguyen (University of Massachusetts, Worcester, Massachusetts, United States) Z Zinger Yang Loureiro (Broad Institute of MIT and Harvard, Boston, Massachusetts, United States) A Amruta Samant (UMass Chan Medical School, Natick, Massachusetts, United States) A Anand Desai (UMass Chan Medical School, Natick, Massachusetts, United States) T Tiffany DeSouza (UMass Chan Medical School, Natick, Massachusetts, United States) H Haley Cirka (UMass Chan Medical School, Natick, Massachusetts, United States) M Mai Ceesay (UMass Chan Medical School, Wocester, Massachusetts, United States) D David Kostyra (UMass Chan Medical School, Natick, Massachusetts, United States) S Shannon Joyce L Lyne Khair (UMass Chan Medical School, Natick, Massachusetts, United States) J Javier Solivan-Rivera (UMass Chan Medical School, Natick, Massachusetts, United States) R Rachel Ziegler (UMass Chan Medical School, Natick, Massachusetts, United States) N Natalia Ketelut Carneiro (UMass Chan Medical School, Natick, Massachusetts, United States) L Linus Tsai (BETH ISRAEL DEACONESS MEDICAL, Boston, Massachusetts, United States) B Brehm Michael (UMass Chan Medical School, Natick, Massachusetts, United States) K Katherine Fitzgerald (UMass Chan Medical School, Natick, Massachusetts, United States) E Evan Rosen (BETH ISRAEL DEACONESS MEDICAL, Boston, Massachusetts, United States) S Silvia Corvera (UMass Chan Medical School, Wocester, Massachusetts, United States)

Abstract

During peripheral vascular disease and 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 pro-inflammatory gene signatures. To further investigate these niches, we developed an in-vitro organoid system that recapitulates key features of the human bone marrow. Progenitor cells from BMY exhibited enriched expression of the leptin receptor, and responded to leptin with increased proliferation and monocyte production. These findings suggest that the age-associated expansion of bone marrow adipose tissue promotes a pro-inflammatory state by stimulating monocyte production from a spatially distinct, leptin-responsive hematopoietic stem/progenitor cell population.

View Original

APA MLA Chicago BibTeX RIS

Article Details

Journal Circulation

Volume / Issue Vol. 152, Issue Suppl_3

Published November 04, 2025

DOI 10.1161/circ.152.suppl_3.4363142

ISSN 0009-7322

Publisher Lippincott Williams & Wilkins

Journal Info

Circulation

Lippincott Williams & Wilkins

ISSN: 0009-7322 Health Sciences

Authors (18)

T

Tammy Nguyen

University of Massachusetts, Worcester, Massachusetts, United States

Z

Zinger Yang Loureiro

Broad Institute of MIT and Harvard, Boston, Massachusetts, United States

A

Amruta Samant