title: Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro.
abstract: 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.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, M5R 1A8, Canada. phillip.karpowicz@utoronto.ca
authors.forename: Phillip
authors.initials: P
authors.lastname: Karpowicz
authors.forename: Cindi
authors.initials: C
authors.lastname: Morshead
authors.forename: Angela
authors.initials: A
authors.lastname: Kam
authors.forename: Eric
authors.initials: E
authors.lastname: Jervis
authors.forename: John
authors.initials: J
authors.lastname: Ramunas
authors.forename: John
authors.initials: J
authors.lastname: Ramuns
authors.forename: Vincent
authors.initials: V
authors.lastname: Cheng
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: 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*
chemical_list: D000963:Antimetabolites; D015415:Biomarkers; D004247:DNA; D001973:Bromodeoxyuridine