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. 2018 Aug 30;11(3):770–783. doi: 10.1016/j.stemcr.2018.08.006

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© 2018 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

Lineage-Specific Markers Highlight Acquisition of Divergent Cell Fates by NSCs Located in Different dSVZ Subdomains

(A and B) Heatmaps show enrichment of transcripts in NSCs of distinct SVZ regions (dmNSCs, dlNSCs, lNSCs) compared with the dorsal environment (dSVZ). Transcripts of stem cell, proliferation, and neurogenesis markers (A; top panel) and selected signaling pathways (A; bottom panel) were analyzed. Selected markers of the astroglial (B; top panel), oligodendroglial (B; middle panel), and neuronal lineage (B; bottom panel) were analyzed. Astrocyte and neuronal markers show regional enrichment in dmNSCs and dlNSCs, respectively, while oligodendroglial markers show partial preference for enrichment in dmNSC. Note that HOPX transcripts were enriched in dmNSCs.

(C) Scheme representing the counter gradients of the expression of Hopx (red) and astroglial markers (yellow) against the expression of neuronal markers (green) in dNSCs. Oligodendroglial markers (blue) do not show such a clear spatial gradient.

(D) dmEPO and dlEPO highlight divergent lineage outputs of the two dorsal subdomains. The scheme shows the orientation of the electrodes for the targeted EPOs at P2 followed by analysis at 14 dpe.

(E–G) Representative micrographs of OB sections after dmEPO and dlEPO (E and F). Cell counts of OB neurons indicate that neurogenesis of the dSVZ mainly originates from dlNSCs (G).

(H–J) Representative micrographs of LV containing sections after dmEPO and dlEPO. Cells with an astrocytic fate were identified according to their morphology and GFAP expression (H and I, arrows indicate double positive cells). Quantification of astrocytes indicate that astrogenesis of the dSVZ is mainly provided by dmNSCs (J).

(K) Graph showing the fractions of astroglial and neuronal progenies from NSCs of these two subdomains. It highlights that dmNSCs are primed for generating astrocytes, whilst neurons are derived from dlNSCs.

dpe, days post electroporation; dSVZ, dorsal SVZ; dmNSCs, dorsomedial NSCs; dlNSCs, dorsolateral NSCs; lNSCs, lateral NSCs; EPO, electroporation. Animals: (A) 4–5 per n; (B) dmEPO, n = 4; (B) dlEPO, n = 5. Error bars represent SEM. Scale bars in (F) and (I) represent 200 μm (overviews) and 25 μm (crops), and apply also to (E) and (H). ^∗p < 0.05; ^∗∗∗p < 0.001; ^∗∗∗∗p < 0.0001.