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Purification of a pluripotent neural stem cell from the adult mouse brain

Abstract

The adult mammalian central nervous system (CNS) contains a population of neural stem cells (NSCs)1,2,3,4 with properties said to include the generation of non-neural progeny5,6,7. However, the precise identity, location and potential of the NSC in situ remain unclear. We purified NSCs from the adult mouse brain by flow cytometry, and directly examined the cells' properties. Here we show that one type of NSC, which expresses the protein nestin but only low levels of PNA-binding and HSA proteins, is found in both ependymal and subventricular zones and accounts for about 63% of the total NSC activity. Furthermore, the selective depletion of the population of this stem cell in querkopf8 mutant mice (which are deficient in production of olfactory neurons) suggests that it acts as a major functional stem cell in vivo. Most freshly isolated NSCs, when co-cultured with a muscle cell line, rapidly differentiated in vitro into myocytes that contain myosin heavy chain (MyHC). This demonstrates that a predominant, functional type of stem cell exists in the periventricular region of the adult brain with the intrinsic ability to generate neural and non-neural cells.

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Figure 1: Flow cytometric purification of NSCs.
Figure 2: PNAlo HSAlo adult NSCs give rise to neural and muscle cell types.

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Acknowledgements

This work was supported by grants from the NH-MRC of Australia, the Australasian Spinal Research Trust, and the Motorneuron Disease Research Institute. We express our gratitude to P. Tam for supplying BU5X mice; S. S. Tan for transplantation assistance; E. Hardeman for supply and assistance with C2C12 myocytes and muscle-specific antibodies and J. Coonan for assistance with microinjections.

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Correspondence to Perry F. Bartlett.

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Rietze, R., Valcanis, H., Brooker, G. et al. Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 412, 736–739 (2001). https://doi.org/10.1038/35089085

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