Overview of hypoxic peri-arteriolar HSC niches in bone marrow (A–C) and
hypoxic peri-arteriolar GSC niches in gliobastoma (D–F). Rectangles in A
(salmon and green) indicate peri-arteriolar and peri-sinusoidal regions in
bone marrow shown in B and C, respectively. Rectangles in D (salmon and
green) indicate peri-arteriolar and peri-capillary regions in glioblastoma
shown in E and F, respectively. HE staining of human bone marrow (A) shows a
peri-arteriolar HSC niche (B) and peri-sinusoidal progenitor cells around
sinusoids (A, C) and HE staining of human glioblastoma (D) shows a
peri-arteriolar GSC niche (E) and differentiated glioblastoma cells around
capillaries (F). HSCs express CD150, CD133, CXCR4, CD44 and HIF-1/2α and
GSCs express CD133, SOX2 CXCR4, CD44 and HIF-2α. HSCs and GSCs are localized
around SMA-positive arterioles in niches where chemoattractants SDF-1α and
OPN are abundantly and exclusively expressed. SDF-1α-CXCR4 and OPN-CD44
facilitate retention of HSCs and GSCs in their niches. MSCs with
intracellular SDF-1α and OPN express CD105, CD73 and STRO-1 and are
exclusively localized in peri-arteriolar HSC and GSC niches. VEGF is widely
expressed in bone marrow and glioblastoma (B, E). At distance from bone,
hematopoietic progenitor cells expressing CD244, CXCR4 and CD44 are
localized around sinusoids (C). Differentiated glioblastoma cells express
CXCR4 and CD44 are localized around capillaries (F). Scale bar A = 200 µm;
scale bar D = 100 µm. Abbreviations: HSC, hematopoietic stem cell; GSC,
glioblastoma stem cell; HE, Hematoxylin-eosin; CXCR4, C-X-C receptor type 4;
HIF, hypoxia-induced factor; SOX2, sex determining region Y-box 2; SMA,
smooth muscle actin; SDF-1α, stromal-derived factor-1α; OPN, osteopontin;
VEGF, vascular endothelial growth factor; MSC, mesenchymal stem cell;
STRO-1, stromal factor-1; OB, osteoblast; ta, tunica adventitia; tm, tunica
media.