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Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke

http://www.cell.com/cell-stem-cell/abstract/S1934-5909(15)00357-4?rss=yes by

 

Figure 1

Migratory SVZ Cells Give Rise to Neurospheres in the Stroke-Injured Cortex

(A) Experimental design for cortical NS culture.

(B) SVZ derived and cortical derived NSs (svz and ctx).

(C) Number of NSs formed from the uninjured and stroke-injured cortex and SVZ (∗∗ = p = 0.001, unpaired t test with Welch’s correction, t(8) = 5.006, data represent ±SEM, nctx = 11 mice, and nsvz = 9 mice).

(D) Diagram of injection sites lateral and caudal to the original sensory-motor cortex lesion site.

(E) Number of NSs formed from the cortex and SVZ in lesions lateral and caudal to the original sensory-motor cortex lesion (smctx) and after PVD (∗∗∗ = p < 0.001, unpaired t test, t(12) = 9.785, data represent ±SEM, nsmctx_ctx = 9 mice, nsmctx_SVZ = 5 mice; ∗∗∗ = p < 0.001, unpaired t test, t(6) = 8.454, data represent ±SEM, nlat_ctx = 4 mice, nlat_SVZ = 4 mice;  = p < 0.05, unpaired t test, t(4) = 3.908, data represent ±SEM, ncaud_ctx = 3 mice, ncaud_SVZ = 3 mice; and  = p < 0.05, unpaired t test, t(12) = 2.978, data represent ±SEM, nPVD_ctx = 7 mice, nPVD_SVZ = 7 mice).

(F) Number of NSs at passage 4 and passage 10 from the original sensory-motor cortex lesion, lateral, and caudal to that site and after PVD (n.s., unpaired t test, t(5)passage4_et-1 = 0.1879, t(11)passage10_et-1 = 1.1016, t(12)passage4_PVD = 0.3755, t(10) passage10_PVD = 1.910, t(3) passage4_lat = 0.07205, t(2) passage10_late = 0.112, t(4) passage4_caud = 1.349, t(4) passage10_caud = 0.9843, data represent ±SEM, nP4_et1_ctx = 3, nP10_et1_ctx = 6, nP4_PVD_ctx = 7, nP10_PVD_ctx = 7, nP4_lat_ctx = 2, nP10_lat_ctx = 2, nP4_caud_ctx = 2, nP10_caud_ctx = 2, nP4_et1_SVZ = 4, nP10_et1_SVZ = 7, nP4_PVD_SVZ = 6, nP10_PVD_SVZ = 6, nP4_lat_SVZ = 3, nP10_lat_SVZ = 2, nP4_caud_SVZ = 4, and nP10_caud_SVZ = 4, 3 independent trials).

(G) Lineage tracing of SVZ cells using Nestin-CreERT2;tdTomatofl;hGFAP-GFP mice. The picture shows tdTOMATO expression in ctxNSs.

(H) Lineage tracing of SVZ cells using Nestin-CreERT2;YFPfl mice. The pictures show YFP expression in ctxNSs and SVZNSs.

(I) YFP expression in ctxNSs from stroke sites lateral and caudal to the original sensory-motor cortex lesion site and PVD.

(J) AraC ablation paradigms.

(K) Number of ctxNSs and svzNSs after AraC ablation (∗∗ = p < 0.01, ∗∗∗ = p < 0.001, one-way ANOVA with Tukey’s post hoc, F (2,11) = 16.91, data represent ±SEM from (days, d) nsaline = 8, n14dAraC = 4, and n10dAraC = 2.

(L) KI-67 positive cells in the cortex (uninjured = uninj, injured = inj, subventricular zone = SVZ, lateral ventricle = lv, cortex = ctx, corpus callosum = cc, sensory-motor cortex = smctx, PVD, lateral = lat, caudal = caud, tdTOMATO = TOM, and tamoxifen = TAM). See also Figure S1 and Table S1 .