Investigating the Perivascular Haematopoietic Stem Cell Niche in Adult Bone Marrow under Healthy Conditions versus Stress

Abstract

Haematopoiesis is the process of blood production arising from haematopoietic stem cells (HSCs) that reside in a bone marrow (BM) microenvironment known as the HSC niche. BM perivascular niche primarily comprises of endothelial and perivascular cells supporting HSC maintenance and proliferation. Haemogenic endothelium (HE) is a specialised endothelial cell (EC) type that gives rise to HSCs, hence mature blood cells. This phenomenon has been reported in embryonic mouse tissues, such as the yolk sac (YS), dorsal aorta (DA), and placenta. However, what gives rise to de novo HSCs in adult BM remains a mystery. Given that the role of ECs toward HSCs in the perivascular niche is critical, our research primarily investigates whether BM endothelium supports the HSC niche in adult BM under healthy and stress conditions. Flow cytometric results show that haemolytic anaemia, IRF-8 deficiency and complete myelosuppression of adult BM affects EC frequency. Also, HSCs of myelosuppressed and IRF-8-deficient BM demonstrated a change in frequency and absolute number, respectively. Further investigation of EC subpopulations illustrated that VE-cadherin+ ECs co-express CD11b myeloid marker, B220 lymphoid marker, Ter-119 erythroid marker, and CD45 mature haematopoietic marker. IRF-8 deficiency alters absolute number of BM VE-cadherin+ endothelial subpopulations. Our study has shown that ECs and HSCs suffer alteration under certain BM stress models. Moreover, it raises the question as to whether EC subpopulations are the BM version of haemogenic endothelium found in the embryo. Further studies are required for the characterisation of these cells in vitro. Successful production of lineagespecific cells from each endothelial sub-cell type would generate a promising prospect to future regenerative therapies in vivo.