Molecular cascade reveals sequential milestones underlying hippocampal neural stem cell development into an adult state

• Published in: Cell reports (Cambridge) Vol. 43; no. 6; p. 114339
• Main Authors: Jimenez-Cyrus, Dennisse, Adusumilli, Vijay S., Stempel, Max H., Maday, Sandra, Ming, Guo-li, Song, Hongjun, Bond, Allison M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.06.2024; Elsevier
• Subjects: adult stem cells; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Autophagy; Cell Differentiation; Cell Proliferation; cell state transition; cellular metabolism; CP: Cell biology; CP: Neuroscience; dentate gyrus; Dentate Gyrus - cytology; Dentate Gyrus - growth & development; Dentate Gyrus - metabolism; hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Mice; Mice, Inbred C57BL; neural development; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; quiescence; Reactive Oxygen Species - metabolism; Single-Cell Analysis; dentate gyrus; hippocampus; CP: Cell biology; CP: Neuroscience; cellular metabolism; Neural stem cells; quiescence; neural development; cell state transition; adult stem cells
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114339

Quiescent adult neural stem cells (NSCs) in the mammalian brain arise from proliferating NSCs during development. Beyond acquisition of quiescence, an adult NSC hallmark, little is known about the process, milestones, and mechanisms underlying the transition of developmental NSCs to an adult NSC state. Here, we performed targeted single-cell RNA-seq analysis to reveal the molecular cascade underlying NSC development in the early postnatal mouse dentate gyrus. We identified two sequential steps, first a transition to quiescence followed by further maturation, each of which involved distinct changes in metabolic gene expression. Direct metabolic analysis uncovered distinct milestones, including an autophagy burst before NSC quiescence acquisition and cellular reactive oxygen species level elevation along NSC maturation. Functionally, autophagy is important for the NSC transition to quiescence during early postnatal development. Together, our study reveals a multi-step process with defined milestones underlying establishment of the adult NSC pool in the mammalian brain. [Display omitted] •NSC development into an adult state is a multi-step process with defined milestones•Molecular cascade underlying NSC quiescence acquisition and subsequent maturation•Sequential metabolic changes in autophagy and ROS during NSC development•Autophagy promotes NSC quiescence during early postnatal development Jimenez-Cyrus et al. report the molecular cascade underlying the neural stem cell transition to the quiescent adult state in the early postnatal mouse dentate gyrus. Neural stem cells sequentially progress through multiple states accompanied by transcriptional and metabolic changes. Autophagy functionally promotes the neural stem cell transition to quiescence.