Impact of partial reprogramming, aging, and differentiation on primary neural stem cells

Partial reprogramming is of interest as a potential strategy to improve or erase aging hallmarks. The mechanisms underlying its effect on specific cell types remain unknown. Here, we investigate early transcriptional changes that could mediate the effects of reprogramming on old neural stem cells (NSCs) and their differentiation. To investigate early transcriptional changes that could underlie the impact of partial reprogramming on the function of old neural stem cells, we isolated primary neural stem cells from young (3-4 months; n=5) and old (25 months; n=4) transgenic mice. We performed bulk RNA-seq for a time course of partial reprogramming in neural stem cells (3 time points) and during differentiation (3 time points). Differential expression analysis reveals genes that change during differentiation to neuronal and glial lineages; genes that differ with aging; and age-associated changes that are restored by partial reprogramming at various time points.