Megakaryocytes as the Regulator of the Hematopoietic Vascular Niche

Abstract

Megakaryocytes (MKs) are important components of the hematopoietic niche. Compared to the non-hematopoietic niche cells, MKs serving as part of the hematopoietic niche provides a mechanism for feedback regulation of hematopoietic stem cells (HSCs), in which HSC progeny (MKs) can modulate HSC adaptation to hematopoietic demands during both steady-state and stress hematopoiesis. MKs are often located adjacent to marrow sinusoids. Considering that most HSCs reside close to a marrow vascular sinusoid, as do MKs, the interactions between MKs and vascular endothelial cells are positioned to play important roles in modulating HSC function, and by extrapolation, might be dysregulated in various disease states. In this review, we discuss the interactions between MKs and the vascular niche in both normal and neoplastic hematopoiesis.

Keywords: hematopoietic microenvironment; hematopoietic stem cell (HSC); megakaryocyte (MK); myeloproliferative neoplasms; vascular niche.

Figure 1

Immunofluorescence staining and deep confocal imaging of marrow MK-EC interactions. (A) Representative confocal images of wild-type control (left) and Tie2⁺FF1⁺ (right) mouse femur marrow stained with antibodies against CD41 (red) and laminin (green). (B) Quantitative analysis revealed increased area of contact between MKs and sinusoid vessels in the marrow of Tie2⁺FF1⁺ mice compared to the control mice. Two control mice and two Tie2⁺FF1⁺ mice were used and a total of 10 high-quality non-overlapping areas at 20x magnification were selected for analysis with the ImageJ software (National Institute of Health, Bethesda, MD, USA). * P < 0.05.

Figure 2

Representative whole-mount confocal images of aged wild-type control (A) and Pf4⁺FF1⁺ (B) mouse femur marrow, in which the vasculature was stained intravenously with anti-VE-cadherin antibody before euthanization. Images were acquired with an Olympus IX81 microscope using 20x objective magnification and Olympus Fluoview FV1000 confocal laser scanning system at 512 x 512 pixel resolution.