Dissecting the spatial bone marrow microenvironment of hematopoietic stem cells.

Abstract

Hematopoietic stem cells (HSCs) reside in specialized anatomical microenvironments within the bone marrow space, termed HSC niches. Different bone marrow imaging modalities have been utilized to visualize HSCs in situ, and unravel the cellular identity of bone marrow cell types located in their immediate proximity. However, despite extensive research, the exact identity of bone marrow populations that physically associate with HSCs remains controversial. Recent advances in volumetric imaging enable precise identification of bone marrow populations and their spatial distribution both at tissue-wide scale and single-cell resolution. In addition, single-cell RNA sequencing and mass-cytometry-based approaches dissect the complexity of the bone marrow microenvironment with unprecedented resolution. Here, we review current concepts regarding bone marrow populations that physically associate with HSCs and recent efforts to localize HSCs and their niche populations. Defining the bone marrow cell types in the immediate proximity of HSCs in homeostasis and stress is key to determine the cellular and molecular cues driving HSC maintenance and regeneration.