Shining a light on hematopoietic stem cells

Abstract

A combination of light and electron microscopy has revealed further details about the location and interactions of hematopoietic stem and progenitor cells.

Keywords: correlative light; developmental biology; dopamine beta-hydroxylase; electron microscopy; hematopoietic stem cell; microenvironment; regenerative medicine; serial section blockface scanning electron microscopy; stem cell niche; stem cells; zebrafish.

Figure 1.. Visualizing hematopoietic stem cells in their developmental niches.

(A) A zebrafish embryo 48 hours post fertilization (48 hpf) showing the dorsal aorta (thick red line) and vein (thick blue line) and the caudal hematopoietic tissue (CHT). Hematopoietic stem cells (HSCs) emerge from the dorsal aorta (downward red arrows) and then circulate via blood flow (blue and red lines with arrowheads), before settling in the CHT, where they start to multiply. (B) Subsequently, hematopoietic stem and progenitor cells (HSPCs) exit the CHT to settle into secondary niches, such as the thymus (turquois shape) and the kidney marrow (green rectangle; the grey round shape is the swim bladder). Agarwala et al. have used five-day-old larvae (5dpf) to visualize HSPCs in the diverse niches of the kidney marrow (ROI, region of interest; g, glomerulus), using live fluorescence microscopy. Automatic serial sectioning of the ROI generated about 3,000 sections, each of which was imaged at electron microscopic resolution (SBEM). Computer-assisted image treatment allowed to superposition fluorescence and electron micrographs images to identify HSPCs on 2D SBEM sections, to obtain high resolution 3D datasets (purple), and to visualize the entire HSPC contacting surfaces. This showed that in the perivascular region, HSPCs interact with contacting cells, such as ganglion-like cells (GL, red), a unique mesenchymal stromal cell (MSC, orange) and up to five endothelial cells (ECs).