Endogenous Adult Neural Stem Cells Comprise The Minority of Label Retaining Cells in the Adult Mouse Brain

Objective: Given rapidly dividing and slow cycling populations of neural precursors have been identified in the adult brain, with several lines of evidence suggesting the later population represents Neural Stem Cells (NSCs), we hypothesized that adult NSCs could be identified using Label Retaining Cell (LRC) approach. Materials and Methods: Adult CBA mice were injected with the mitotic marker bromodeoxyuridine (BrdU), every two hours for 48 hours. We compared the number of LRCs detected in a 400µm region of the PVR at increasing chase periods to the number of primary neurospheres and NSC-derived colonies (Large Colonies) that could be generated from the same region using Neurosphere Assay (NSA) and Neural Colony-Forming Cell Assay(N-CFCA). Results: While the prevalence of LRCs and neurospheres and overall colonies was equivalent at specific chase periods,the number of NSC-derived colonies remained reduced by at least two orders of magnitude for chase periods up to 7 months. Conclusion: Our results suggest that < 5% of LRCs are bona fide neural stem cells and highlights the pitfalls of employing this methodology to discern stem from progenitor cell populations