Abstract
Continuous generation of blood cells over an organism's lifetime is supported by hematopoietic stem/progenitor cells (HSPCs) capable of producing all hematopoietic cell subtypes. Adult mammalian HSPCs are localized to bone marrow and regulated by their neighboring microenvironment, or “niche.” Because interactions of HSPCs with their niches are highly dynamic and complex, the recent development of imaging technologies provides a powerful new tool to understand stem cell/niche biology. In this review, we discuss recent advances in our understanding of dynamic HSPC/niche interactions during development, homeostasis, disease states or aging with a focus on studies advanced by imaging analysis. We also summarize methods to visualize HSPCs and niche cells in vivo, including use of HSPC reporter mice and chemical probes. Findings emerging from these investigations could suggest novel therapies for diseases and aging.
Highlights
A lifetime supply of mature blood cells by a process known as hematopoiesis is maintained by differentiation and proliferation of hematopoietic stem/progenitor cells (HSPCs) in response to physiological or pathological stimuli
Analysis of Ly6a (Sca-1)-GFP transgenic mice, in which HSPCs are GFP-positive (Ma et al, 2002), combined with 3D confocal microscopy, has revealed the precise timing of hematopoietic stem cells (HSCs) emerging can be visualized at the embryonic aortic endothelium (Boisset et al, 2010)
This study shows that blood flow profiles modulate HSPC homing in the bone marrow vasculature and employs calvaria and femur for in vivo imaging and FACS analysis, respectively
Summary
A lifetime supply of mature blood cells by a process known as hematopoiesis is maintained by differentiation and proliferation of hematopoietic stem/progenitor cells (HSPCs) in response to physiological or pathological stimuli. Microscopic analysis has helped define HSC niche structure (Table 1): briefly, confocal microscopy is used to scan bone marrow sections stained immunohistochemically and provides clear image at high speed (Joseph et al, 2013). Mice created using knock-in of a reporter driven by the RNA-binding protein Musashi2 (Msi2) enabled confocal laser scanning microscopy analysis of HSPC movement in calvarial bone marrow (Koechlein et al, 2016); that study revealed that HSPCs residing near vessels migrate toward close proximity to endosteum (Figure 1).
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