Fig 2: IGFBPL1 in the human SVZ.a In left panel, dot plot representing the gene activity of selected genes in three cell populations (FIB: fibroblasts, iPS: induced Pluripotent Stem cells, iPS-NPC: Neural Precursor Cells derived from iPS); each gene is marked by its gene symbol and the genomic coordinates used to derive the gene activity score and the dot size is proportional to the fraction of cells with non-zero signal in the population. Colour code and bubble size represent the mean intensity and % cell fraction of the gene activity score, respectively. In right panel, pseudobulk scATAC-seq profiles over Igfbpl1 locus in three cell populations; each track represents the average ATAC-seq signal of two individuals in separate cell populations and data values are scaled to the number of cells used to derive the profile. In addition to the Igfbpl1 gene structure, the set of DNAseI Hypersensitive Sites (DHS Index) is also represented. b UMAPs showing the three different populations: fibroblast, iPSs and iPS-derived NPCs and the expression of Igfbpl1. c UMAPs showing scRNAseq clusters of iPS-NPCs expressing different levels of Igfbpl1, Nestin and Pax6. d Quantitative PCR of Nestin, Pax6 and Igfbpl1 expressed gene in fibroblasts, iPS and iPS-derived NPCs obtained from three different healthy subjects (n = 3 biologically independent samples). Values represent mean ± SEM. *p = 0.0169, ***p = 0.0008, *p = 0.0369 for Nestin; **p = 0.0042, **p = 0.0086 for Pax6; **p = 0.0066, ***p = 0.0009 for Igfbpl1. One-way ANOVA followed by Tukey post-test. Immunofluorescent staining showing IGFBPL1 (in red) and NESTIN (in green) expression in iPS-derived NPCs from healthy subject. Scale bar: 20 µm. e Quantitative PCR of Igfbpl1 expressed gene in human foetal NPCs. Values represent the mean ± SEM of three technical replicates. f Representative human periventricular brain section showing the SVZ cells lining the ventricle consistently expressing IGFBPL1. IGFBPL1 (brown) and NESTIN (blue) double positive cells are shown. Counterstaining with haematoxylin. Different magnifications are represented in f’ (×20), f” (×40) and f”’ (×100). The ribbon containing NPCs is highlighted in red. Scale bar: 100 µm in f, 500 µm in f’, 25 µm in f” and 10 µm in f”’. n = 2 samples. Source data are provided as a Source Data file.

Fig 3: IGFBPL1 expression in the mouse SVZ.a Representative confocal images of NestinGFPTK coronal brain sections obtained at the level of the dorsal SVZ, of the ventral SVZ (lateral ventricle), of the thalamus and cortex. Slides were labelled for GFP in green, IGFBPL1 in red and NeuN in white. Nuclei in blue were stained by DAPI. Scale bar: 50 µm. The insert (white square) represents the double positive cells. The same result was obtained in three independent stainings. b Representative confocal images of the striatum and SVZ of NestinTK- and NestinTK+ mice treated with GCV and stained for IGFBPL1 in red. Nuclei in blue were stained by DAPI. Scale bar: 100 µm. The same result was obtained in three independent stainings. c Representative confocal images of the SVZ of NestinTK- and NestinTK+ mice treated with GCV and stained for DCX or BrdU in green, IGFBPL1 in red. Nuclei in blue were stained by DAPI. Scale bar: 50 µm. The graph shows the quantification of the Igfbpl1 in the SVZ of NestinTK- and NestinTK+ mice treated with GCV. n = 3 mice per group. Values represent mean ± SEM. ***p = 0.0002. Unpaired two-tailed t-test. d Representative confocal images of the SVZ of wt mice labelled for IGFBPL1 in red, DCX, BrdU, GFAP and MBP in green. Nuclei in blue were stained by DAPI. The inserts (white square) represent the double positive cells. Scale bar: 50 µm. The same result was obtained in three independent stainings. Source data are provided as a Source Data file.

Fig 4: Gene expression analysis in the SVZ in NestinTK+GCV+ mice.a Workflow of RNA-seq gene expression analysis in control (NestinTK-PBS+, NestinTK-GCV+, NestinTK+PBS+) and NestinTK+GCV+ treated mice. b Heatmap with hierchical clustering of expression values of 115 downregulated genes and 66 upregulated genes with =2-fold change in control and NestinTK+GCV+ mice. (blue means downregulation, red upregulation) n = 5 mice per group. c The graphs represent the top 10 downregulated (in blue) and upregulated (in red) genes. d GSEA curve of genes expressed differentially in NestinTK+GCV+ mice compared to control mice. Enrichment plot for NABA-Matrisome. (FDR = 0.04; NES = -2.5). e Quantitative PCR validation of Igfbpl1 expressed gene in control mice compared with NestinTK+GCV+ mice. n = 10 ctrl mice and n = 5 NestinTK+GCV+ mice. Values represent mean ± SEM. ***p = 0.0027. Mann–Whitney U test, Two-tailed. Source data are provided as a Source Data file.