Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow

Area of Science:

• Hematology
• Aging Biology
• Microenvironment Research

Background:

• Age-related clonal hematopoiesis increases myeloid malignancy risk.
• The bone marrow microenvironment influences this risk, but its aging-related spatial changes are poorly understood.

Purpose of the Study:

• To investigate age-related changes in human bone marrow spatial architecture.
• To explore the relationship between bone marrow fat, hematopoietic stem/progenitor cells (HSPCs), and myeloid cells in aging.

Main Methods:

• Analysis of human bone marrow samples from aging individuals.
• Quantification of bone marrow adiposity, myeloid cell density, HSPC density, and spatial relationships.
• Assessment of NGFR+ bone marrow stromal cell (NGFR+ BMSC) density and proximity to HSPCs and vessels.

Main Results:

• Bone marrow adiposity significantly increases with age.
• Increased adiposity correlates with higher densities of maturing myeloid cells and CD34+ HSPCs.
• A greater proportion of HSPCs are found adjacent to adipocytes in aging bone marrow, while NGFR+ BMSC density and distances to HSPCs/vessels remain stable.

Conclusions:

• Aging bone marrow exhibits increased adiposity and altered spatial arrangements of hematopoietic cells.
• Increased proximity of HSPCs to adipocytes may promote myeloid skewing in aging.
• These microenvironmental changes could contribute to the age-related risk of myeloid malignancies.