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.
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29 August 2005
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August 22 2005
Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro
Phillip Karpowicz,
Phillip Karpowicz
1Institute of Medical Science, University of Toronto, Toronto, M5R 1A8, Canada
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Cindi Morshead,
Cindi Morshead
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
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Angela Kam,
Angela Kam
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
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Eric Jervis,
Eric Jervis
4Department of Chemical Engineering, University of Waterloo, Waterloo, N2L 3G1, Canada
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John Ramunas,
John Ramunas
4Department of Chemical Engineering, University of Waterloo, Waterloo, N2L 3G1, Canada
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Vincent Cheng,
Vincent Cheng
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
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Derek van der Kooy
Derek van der Kooy
3Department of Medical Genetics and Microbiology, University of Toronto, Toronto, M5R 1A8, Canada
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Phillip Karpowicz
1Institute of Medical Science, University of Toronto, Toronto, M5R 1A8, Canada
Cindi Morshead
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
Angela Kam
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
Eric Jervis
4Department of Chemical Engineering, University of Waterloo, Waterloo, N2L 3G1, Canada
John Ramunas
4Department of Chemical Engineering, University of Waterloo, Waterloo, N2L 3G1, Canada
Vincent Cheng
2Department of Surgery, University of Toronto, Toronto, M5R 1A8, Canada
Derek van der Kooy
3Department of Medical Genetics and Microbiology, University of Toronto, Toronto, M5R 1A8, Canada
Correspondence to P. Karpowicz: [email protected]
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.
Received:
February 11 2005
Accepted:
July 15 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 170 (5): 721–732.
Article history
Received:
February 11 2005
Accepted:
July 15 2005
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This article has been corrected
Correction: Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro
Citation
Phillip Karpowicz, Cindi Morshead, Angela Kam, Eric Jervis, John Ramunas, Vincent Cheng, Derek van der Kooy; Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro . J Cell Biol 29 August 2005; 170 (5): 721–732. doi: https://doi.org/10.1083/jcb.200502073
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