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Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations

Abstract

The concept of stem-cell plasticity received strong support from a recent observation that extensively passaged, clonally derived neural stem cells could contribute to hematopoiesis. We investigated whether hematopoietic potential was a consistent or unusual feature of neural stem cells, and whether it depended on the extent of in vitro passaging before transplantation. Here we transplanted over 128 × 106 neurosphere cells into 128 host animals; however, we never observed contribution to hematopoiesis, irrespective of the number of passages and despite the use of an assay that could detect the contribution of a single blood stem cell to hematopoietic repopulation. Although extensively cultured neurosphere cells continued to generate neural progeny, marked changes in their growth properties occurred, including changes in growth-factor dependence, cell-cycle kinetics, cell adhesion and gene expression. Our results exclude hematopoietic competence as a consistent property of intravenously infused neural stem cells. However, the consistent changes that occurred during extended passaging are compatible with genetic or epigenetic alterations and suggest that rare transformation events may account for the neural-to-blood fate switch originally reported.

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Figure 1: Long-term (LT) cultured spheres display altered growth and adherence characteristics in vitro.
Figure 2: LT-passaged cultures reveal dramatic changes in proliferation kinetics.
Figure 3: Single-sphere passaging reveals altered proliferation kinetics and the ability to generate spheres in the absence of exogenous growth factors.
Figure 4: Extended bulk passaging leads to neurosphere formation in the absence of exogenous growth factors.
Figure 5: Bone marrow colonies.
Figure 6: Transplantation of Gpi1a/a neurosphere cells.

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Acknowledgements

We thank D. Hyam for technical support; V. Tropepe for technical assistance and helpful comments; and W. Stanford for advice on specific detection of transgenic β-gal. This study was supported by operating grants to D.v.d.K. from the Ontario Neurotrauma Foundation, the Canadian Institutes of Health Research (CIHR) and the Stroke Network, and to NNI from the CIHR.

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Correspondence to Cindi M. Morshead.

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Morshead, C., Benveniste, P., Iscove, N. et al. Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat Med 8, 268–273 (2002). https://doi.org/10.1038/nm0302-268

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