Re-activation of neurogenic 2 niches in aging brain

We report development of a Multimodal MERFISH platform which combines spatial transcriptomics with subcellular resolution on the scale of 2,085-genes, indirect immunofluorescence and EdU labeling to mark DNA replication. With it, we identify populations of neural stem cells (NSCs) lining the ventricular wall or within the subgranular zone that in aged mice have entered a quiescent state marked by reduced expression of neurogenic and cell-cycle genes. We demonstrate that transient suppression of RNA binding protein Polypyrimidine-Tract-Binding-Protein (Ptbp1) reactivates dormant NSCs in two neurogenic niches in aged mice, inducing their cycle re-entry, proliferation, and conversion into neurons via a canonical neurogenesis pathway. Some newly formed neurons incorporate into the striatum and acquire transcriptomes characteristic of mature medium spiny neurons. Similar PTBP1-expressing stem cell-like cells are identified in aged human brain, supporting the reactivation of neurogenesis as a potential therapy against age-related neurodegeneration.