Support for the immortal strand hypothesis: neural stem cells partition DNA asymmetrically in vitro

被引:153
作者
Karpowicz, P [1 ]
Morshead, C
Kam, A
Jervis, E
Ramuns, J
Cheng, V
van der Kooy, D
机构
[1] Univ Toronto, Inst Med Sci, Toronto, ON M5R 1A8, Canada
[2] Univ Toronto, Dept Surg, Toronto, ON M5R 1A8, Canada
[3] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5R 1A8, Canada
[4] Univ Waterloo, Dept Chem Engn, Waterloo, ON N2L 3G1, Canada
关键词
D O I
10.1083/jcb.200502073
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
he 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.
引用
收藏
页码:721 / 732
页数:12
相关论文
共 33 条
[1]   Asymmetric inheritance of oxidatively damaged proteins during cytokinesis [J].
Aguilaniu, H ;
Gustafsson, L ;
Rigoulet, M ;
Nyström, T .
SCIENCE, 2003, 299 (5613) :1751-1753
[2]   MUTATION SELECTION AND NATURAL-HISTORY OF CANCER [J].
CAIRNS, J .
NATURE, 1975, 255 (5505) :197-200
[3]   Somatic stem cells and the kinetics of mutagenesis and carcinogenesis [J].
Cairns, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10567-10570
[4]   Does S. pombe exploit the intrinsic asymmetry of DNA synthesis to imprint daughter cells for mating-type switching? [J].
Dalgaard, JZ ;
Klar, AJS .
TRENDS IN GENETICS, 2001, 17 (03) :153-157
[5]   Subventricular zone astrocytes are neural stem cells in the adult mammalian brain [J].
Doetsch, F ;
Caillé, I ;
Lim, DA ;
García-Verdugo, JM ;
Alvarez-Buylla, A .
CELL, 1999, 97 (06) :703-716
[6]  
Freeman MR, 2001, DEVELOPMENT, V128, P4103
[7]  
Imura T, 2003, J NEUROSCI, V23, P2824
[8]   PARENTAL DNA STRANDS SEGREGATE RANDOMLY DURING EMBRYONIC-DEVELOPMENT OF CAENORHABDITIS ELEGANS [J].
ITO, K ;
MCGHEE, JD .
CELL, 1987, 49 (03) :329-336
[9]   PATERNAL DNA STRANDS SEGREGATE TO BOTH TROPHECTODERM AND INNER CELL MASS OF THE DEVELOPING MOUSE EMBRYO [J].
ITO, K ;
MCGHEE, JD ;
SCHULTZ, GA .
GENES & DEVELOPMENT, 1988, 2 (08) :929-936
[10]   NON-RANDOM SISTER CHROMATID SEGREGATION BY CELL TYPE [J].
JABLONKA, P ;
JABLONKA, E .
JOURNAL OF THEORETICAL BIOLOGY, 1982, 99 (03) :427-436