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

Stem Cell Reports. 2020 Aug 11;15(2):317-325. doi: 10.1016/j.stemcr.2020.06.011. Epub 2020 Jul 9.

Abstract

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.

Keywords: BMSCs; CD34+; adipocytes; aging; microenvironment; myeloid; niche; spatial; stem cells; stroma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Antigens, CD34 / metabolism*
  • Bone Marrow Cells / cytology*
  • Cell Differentiation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Middle Aged
  • Myeloid Cells / cytology

Substances

  • Antigens, CD34