Pluripotency and migration/differentiation factors are variably expressed in the <i>Hmgb2−/−</i> SVZ neural stem cell niche.

<p>The protein levels of different factors were examined in SVZ wholemount tissue lysates from wt and <i>Hmgb2</i><b><i>−/−</i></b> mice. A) Oct4; B) pAkt (ser); C) p21 (two representative immunoblots are provided); D) NCAM (n = 3); E) Cartoon depicting the suggested role of HMGB2 in NSC maintenance.</p

Heightened DCX expression in the SVZ of 10 week old <i>Hmgb2−/−</i> mice.

<p>Mash1 and Nestin expression in lateral <i>Hmgb2+/+</i> and <i>Hmgb2−/−</i> brain sections and surface plots of pixel density distributions (A,B). Doublecortin (DCX) in lateral and medial <i>Hmgb2+/+</i> and <i>Hmgb2−/−</i> brain sections (C,D) with quantification of DCX+ cells/SVZ hpf in WT and <i>Hmgb2−/−</i> medial brain sections (E). The values are mean+/− SEM, **p = 0.036.</p

Increase in olfactory bulb granule cell layer neurogenesis in 10 week old <i>Hmgb2−/−</i> mice.

<p>A) Immunostaining for BrdU (red) and NeuN (green) and the merged image in the OB granule cell layer (GCL) of 10 week old mice after 14 days of differentiation. Quantification of (B) BrdU+, (C) NeuN+, and (D) BrdU+/NeuN+ cell densities in the GCL of WT and <i>Hmgb2−/−</i>10 week old mice. Quantification of the relative fraction of newborn GCL neurons (BrdU+/NeuN+) among (E) all BrdU+ cells and (F) all NeuN+ cells. (G) Immunostaining of OB glomerular layer (GL) neurogenesis after 14 days differentiation <i>in vivo</i>. (H-L) Quantification of GL neurogenesis at 2.5 months. All figures are mean+/− SEM, n = 2 WT and n = 3 <i>Hmgb2−/−</i> per group; the Kruskal-Wallis test was used. (p = 0.0008 for panel B), but no significance for all other panels.</p

Hyperproliferation and altered NSC/NPC composition <i>in vivo</i> in 10 week old <i>Hmgb2−/−</i> mice.

<p>A) Immunostaining for BrdU (red) and Ki67 (green) in the anterior SVZ of 10 week old WT and <i>Hmgb2−/−</i> mice. B) Collapsed image of confocal Z-stacks from brain sections of compound <i>Hmgb2+/+</i>NestinGFP+ and <i>Hmgb2−/−</i>NestinGFP+ transgenic mice stained for GFAP, a marker of SVZ NSCs. GFAP (red), Nestin (green), DAPI (blue). (C) High magnification orthogonal view of a single confocal plane from brain sections of compound transgenic mice stained with GFAP at the SVZ/RMS junction. D) Quantification of SVZ BrdU+ cells and cell density in (A), E) Ki67+ cells and cell density in (A), F) BrdU+/Ki67+ cells and cell density in (A). All figures are mean+/− SEM, *p≤0.05, **p≤0.005. n = 4 WT and n = 5 <i>Hmgb2−/−</i> per group. (G) Quantification of Nestin+ and GFAP+ staining in WT and <i>Hmgb2−/−</i> SVZ in (B). All figures are mean+/− SEM; the Kruskal-Wallis test was used. ***p = 0.0002. n = 4 WT and n = 5 <i>Hmgb2−/−</i> per group. (H) Reconstruction of z-stacks used to generate the image in panel B of GFAP staining in the SVZ of <i>Hmgb2+/+</i> (WT) and <i>Hmgb2−/−</i> mice. DAPI (blue), GFAP (red), and Nestin (green).</p