Quiescent neural stem cells in the V-SVZ have been extensively studied and are known to generate newborn neurons throughout adulthood in the mammalian brain. Although previous studies have used different approaches to characterise the diverse cell populations of the V-SVZ, they have overlooked a crucial group of stem cells.
By combining a novel lineage tracer mouse model with fluorescence-activated cell sorting and single-cell RNA sequencing, the researchers revealed a distinct population of quiescent neural stem cells that appears less differentiated and more quiescent than the traditionally accepted GLAST+ B1 cells.
The Minichiello group refers to this newly identified population as B0 cells. These cells are marked by the inward-rectifying potassium channel KiR7.1, the serotonin receptor 5-HT2C, and the prolactin receptor PRLR, among other markers. They have a transcriptional profile consistent with the high mitochondrial oxidative metabolism required to maintain long-term quiescence and appear to lie upstream of the classical GLAST-positive neural stem cells in the developmental trajectory.
Pseudotime analysis indicated that these B0 cells likely represent the earliest stage of the neural stem-cell lineage, preceding progression into conventional quiescent NSCs, progenitors, neuroblasts, and ultimately neurons. The study also demonstrated that this population exhibits a molecular signature conserved across species.
Adult neural stem cells are promising targets for regenerative medicine due to their ability to produce new neurons after injury. This work matters as it suggests that: a) previous studies may have overlooked an important reservoir of adult neural stem cells; b) therapies aimed at activating this deeply quiescent population could enhance endogenous brain repair; c) markers like Htr2c and Prlr could serve as new therapeutic targets to promote neurogenesis in conditions such as Parkinson's disease, stroke, or other neurodegenerative disorders.
While additional functional research is required to establish optimal methods for therapeutic manipulation of these cells, this study overall presents a new type of adult neural stem cells. These cells may be the most primitive quiescent state discovered in the V-SVZ to date and offer a valuable resource for future brain regeneration research.
The study can be accessed here: https://www.nature.com/articles/s41421-026-00914-4