Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro.
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.
Karpowicz
Phillip
P
Institute of Medical Science, University of Toronto, Toronto, M5R 1A8, Canada. phillip.karpowicz@utoronto.ca
Morshead
Cindi
C
Kam
Angela
A
Jervis
Eric
E
Ramunas
John
J
Ramuns
John
J
Cheng
Vincent
V
van der Kooy
Derek
D
D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D020090:Chromosome Segregation; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010375:Pedigree; D016548:Prosencephalon / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D000963:Antimetabolites; D015415:Biomarkers; D004247:DNA; D001973:Bromodeoxyuridine