Extended Data Fig. 5: Impaired lineage progression of fate-committed neural progeny with aging.
a, List of TFs in each pseudotime modules of which the GRN have been successfully reconstructed. b-c, Projection of GRN activity in the pseudotemporal trajectory of addtional transcription factors. Grey bar indicates putative transition zone between aNSPC and NB/IMN. (b) GRN activity of Hes6, Tfdp and E2f1 along the pseudotemporal trajectory. Left: Visualization by the transition from aNSPC to NB/IMN. Right: Visualization by individual ages. (c) GRN activity of Nhlh, Bhlhe22 and Mafb along the pseudotemporal trajectory. Upper: Visualization by the transition from aNSPC to NB/IMN. Lower: Visualization by individual ages. Shading indicates 95% confidence interval. Gray zone indicates the transition from aNSPC to NB/IMN. d, Immunofluorescent staining of SOX2 and neuroblasts (NEUROD1 and DCX) showing this transitional stage of neural progeny differentiation is delayed in advancing ages. e, Quantification of the percentage of SOX2+ neuroblasts among all neuroblasts (NEUROD1+DCX+) at different ages (young: 2.8 ± 0.1%; middle-age: 12.1 ± 0.8%; old: 33.0 ± 2.0%; two-tailed unpaired t-test with Welch’s correction, **P = 0.0012 between young and middle-age, ***P = 0.0001 between middle-age and old, ****P < 0.0001 between young and old). f, Schematic illustration of delayed lineage progression from aNSPC to NB/IMN. aNSPC, active neural stem and progenitor cells, GRN, gene regulatory network and NB/IMN, neuroblast and immature neuron. All data were presented as mean ± SEM. Scale bars, 20 μm.
