Lab-grown brain organoids reveal an intrinsic developmental clock that records years in culture

Researchers cultured human cortical organoids for over five years and found that they age along with in vivo humans, showing transcriptional maturation and DNA methylation changes that track culture time. Epigenetic clocks predicted the organoids’ age with high accuracy, and mixed-age (heterochronic) organoids demonstrated that older progenitors retain a memory of past development and can be steered to produce late-stage neurons, skipping earlier fates. This work positions long-term organoid culture as a powerful in vitro model to study postnatal human brain maturation and neoteny.