Direct conversion to neural stem cells de-ages human blood cells

In human blood cells from donors ranging from neonatal to 101 years of age, researchers tracked cellular rejuvenation during direct lineage conversion into induced neural stem cells. The team overexpressed the reprogramming factors SOX2 and cMYC in erythroid progenitors to generate neural stem cells without passing through an intermediate pluripotent state.

An epigenetic clock algorithm revealed that the direct conversion drove pronounced epigenetic de-aging. This rejuvenation was protracted, continuing over several weeks and persisting even under proliferation-inhibiting conditions. Transcriptomic differences between cells from young and old donors dissipated with extended conversion time, and established lines lacked age-associated cellular hallmarks. Additionally, time-course profiling of DNA methylation and RNA sequencing revealed that gaining a bona fide neural stem cell signature continued well after proliferative, PAX6-positive cells first emerged.