Age-related clonal hematopoiesis is a major risk factor for myeloid malignancy and myeloid skewing is a hallmark of aging. However, while it is known that non-cell-autonomous components of the microenvironment can also influence this risk, there have been few studies of how the spatial architecture of human bone marrow (BM) changes with aging. Here, we show that BM adiposity increases with age, which correlates with increased density of maturing myeloid cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) and an increased proportion of HSPCs adjacent to adipocytes. However, NGFR+ bone marrow stromal cell (NGFR+ BMSC) density and distance to HSPCs and vessels remained stable. Interestingly, we found that, upon aging, maturing myeloid cell density increases in hematopoietic areas surrounding adipocytes. We propose that increased adjacency to adipocytes in the BM microenvironment may influence myeloid skewing of aging HSPCs, contributing to age-related risk of myeloid malignancies.

与年龄有关的克隆性造血是髓系恶性肿瘤的主要危险因素，而髓系偏斜是衰老的标志。然而，虽然已知微环境的非细胞自主成分也可以影响这种风险，但很少有人研究人类骨髓（BM）的空间结构如何随着衰老而变化。在这里，我们显示BM肥胖随着年龄的增长而增加，这与成熟的髓样细胞和CD34 +造血干/祖细胞（HSPC）的密度增加以及与脂肪细胞相邻的HSPC的比例增加有关。但是，NGFR +骨髓基质细胞（NGFR + BMSC）的密度以及与HSPC和血管的距离保持稳定。有趣的是，我们发现，随着年龄的增长，成熟的骨髓细胞密度会在脂肪细胞周围的造血区域增加。