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A correction to this article has been published: Karpowicz et al., J. Cell Biol. 170 (7) 1169
Published online 22 August 2005. doi:10.1083/jcb.200502073
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 5, 721-732
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Article

Support for the immortal strand hypothesis

: neural stem cells partition DNA asymmetrically in vitro



Phillip Karpowicz1, Cindi Morshead2, Angela Kam2, Eric Jervis4, John Ramunas4, Vincent Cheng2, and Derek van der Kooy3

1 Institute of Medical Science, University of Toronto, Toronto, M5R 1A8, Canada
2 Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
3 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, M5R 1A8, Canada
4 Department of Chemical Engineering, University of Waterloo, Waterloo, N2L 3G1, Canada

Correspondence to P. Karpowicz: phillip.karpowicz{at}utoronto.ca

The immortal strand hypothesis proposes that asymmetrically dividing stem cells (SCs) selectively segregate chromosomes that bear the oldest DNA templates. We investigated cosegregation in neural stem cells (NSCs). After exposure to the thymidine analogue 5-bromo-2-deoxyuridine (BrdU), which labels newly synthesized DNA, a subset of neural precursor cells were shown to retain BrdU signal. It was confirmed that some BrdU-retaining cells divided actively, and that these cells exhibited some characteristics of SCs. This asymmetric partitioning of DNA then was demonstrated during mitosis, and these results were further supported by real time imaging of SC clones, in which older and newly synthesized DNA templates were distributed asymmetrically after DNA synthesis. We demonstrate that NSCs are unique among precursor cells in the uneven partitioning of genetic material during cell divisions.

Abbreviations used in this paper: BrdU, 5-bromo-2-deoxyuridine; CFSE, carboxyfluorescein diacetate succinimidyl ester; DiI,1-dioctadecyl-3-tetramethylindocarbocyanine perchlorate; DIV, days in vitro; ESC, embryonic stem cell; GFAP, glial fibrillary acidic protein; ISH, immortal strand hypothesis; NSC, neural stem cell; SC, stem cell.


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