The immortal strand hypothesis: still non-randomly segregating opinions

Abstract Cairns first suggested a mechanism for protecting the genomes of stem cells (SCs) from replicative errors some 40 years ago when he proposed the immortal strand hypothesis, which argued for the inheritance of a so-called immortal strand by an SC following asymmetric SC divisions. To date, the existence of immortal strands remains contentious with published evidence arguing in favour of and against the retention of an immortal strand by asymmetrically dividing SCs. The conflicting evidence is derived from a diverse array of studies on adult SC types and is predominantly based on following the fate of labelled DNA strands during asymmetric cell division events. Here, we review current data, highlighting limitations of such labelling techniques, and suggest how interpretation of such data may be improved in the future.

[1]  W. Bert,et al.  Stem Cells Propagate Their DNA by Random Segregation in the Flatworm Macrostomum lignano , 2012, PloS one.

[2]  Samuel E. Senyo,et al.  Quantitating subcellular metabolism with multi-isotope imaging mass spectrometry , 2011, Nature.

[3]  J. Dalgaard,et al.  Eukaryote DNA replication and recombination : an intimate association , 2011 .

[4]  H. Seligmann,et al.  DNA Replication - Current Advances , 2011 .

[5]  David J. Chen,et al.  Congenital bone marrow failure in DNA-PKcs mutant mice associated with deficiencies in DNA repair , 2011, The Journal of cell biology.

[6]  D. Joubert,et al.  Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation , 2011, Nature communications.

[7]  H. Clevers,et al.  Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes , 2011, The EMBO journal.

[8]  Y. Yamashita,et al.  Drosophila male germline stem cells do not asymmetrically segregate chromosome strands , 2011, Journal of Cell Science.

[9]  G. Babcock,et al.  Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks. , 2010, Stem cells and development.

[10]  F. Kittrell,et al.  Immortalized, premalignant epithelial cell populations contain long-lived, label-retaining cells that asymmetrically divide and retain their template DNA , 2010, Breast Cancer Research.

[11]  Hans Clevers,et al.  Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells , 2010, Cell.

[12]  M. Warr,et al.  Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. , 2010, Cell stem cell.

[13]  Amy Freeland,et al.  Cell Cycle Heterogeneity in the Small Intestinal Crypt and Maintenance of Genome Integrity , 2010, Stem cells.

[14]  T. Graham,et al.  Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer? , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  Allon M. Klein,et al.  The ordered architecture of murine ear epidermis is maintained by progenitor cells with random fate. , 2010, Developmental cell.

[16]  Hans Clevers,et al.  Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. , 2010, Cell stem cell.

[17]  M. Koutsilieris,et al.  Discovery of the mitotic selective chromatid segregation phenomenon and its implications for vertebrate development. , 2010, Current opinion in cell biology.

[18]  Hans Clevers,et al.  Coexistence of Quiescent and Active Adult Stem Cells in Mammals , 2010, Science.

[19]  Curtis C. Harris,et al.  Microenvironmental modulation of asymmetric cell division in human lung cancer cells , 2010, Proceedings of the National Academy of Sciences.

[20]  Peter M. Lansdorp,et al.  Identification of sister chromatids by DNA template strand sequences , 2010, Nature.

[21]  P. Quesenberry,et al.  Heterogeneity of non‐cycling and cycling synchronized murine hematopoietic stem/progenitor cells , 2010, Journal of cellular physiology.

[22]  F. Watt,et al.  Epidermal stem cell diversity and quiescence , 2009, EMBO molecular medicine.

[23]  D. van der Kooy,et al.  The germline stem cells of Drosophila melanogaster partition DNA non-randomly. , 2009, European journal of cell biology.

[24]  P. Lio’,et al.  Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair , 2008, Cell.

[25]  S. Tajbakhsh Stem cell identity and template DNA strand segregation. , 2008, Current opinion in cell biology.

[26]  D. Steindler,et al.  Bromodeoxyuridine Induces Senescence in Neural Stem and Progenitor Cells , 2008, Stem cells.

[27]  C. Blanpain,et al.  The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation , 2008, Stem cells.

[28]  Martin A. White,et al.  Non-random segregation of sister chromosomes in Escherichia coli , 2008, Nature.

[29]  T. Tumbar,et al.  Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells , 2008, The EMBO journal.

[30]  Anindya Dutta,et al.  The Immortal Strand Hypothesis: How Could It Work? , 2008, Cell.

[31]  I. Weissman,et al.  Hematopoietic Stem Cell Quiescence Attenuates DNA Damage Response and Permits DNA Damage Accumulation During Aging , 2007, Cell cycle.

[32]  T. Rando The Immortal Strand Hypothesis: Segregation and Reconstruction , 2007, Cell.

[33]  P. Lansdorp Immortal Strands? Give Me a Break , 2007, Cell.

[34]  Irving L. Weissman,et al.  Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age , 2007, Nature.

[35]  T. Suda,et al.  Maintenance of Quiescent Hematopoietic Stem Cells in the Osteoblastic Niche , 2007, Annals of the New York Academy of Sciences.

[36]  T. Rando,et al.  High Incidence of Non-Random Template Strand Segregation and Asymmetric Fate Determination In Dividing Stem Cells and their Progeny , 2007, PLoS biology.

[37]  A. Klar,et al.  Left-Right Dynein Motor Implicated in Selective Chromatid Segregation in Mouse Cells , 2007, Science.

[38]  J. Tischfield,et al.  Protecting genomic integrity in somatic cells and embryonic stem cells. , 2007, Mutation research.

[39]  Barbara Gayraud-Morel,et al.  Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells , 2006, Nature Cell Biology.

[40]  D. van der Kooy,et al.  Support for the immortal strand hypothesis , 2005, The Journal of cell biology.

[41]  Gilbert H. Smith,et al.  Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands , 2005, Development.

[42]  A. Klar A Genetic Mechanism Implicates Chromosome 11 in Schizophrenia and Bipolar Diseases , 2004, Genetics.

[43]  M. Fuller,et al.  Orientation of Asymmetric Stem Cell Division by the APC Tumor Suppressor and Centrosome , 2003, Science.

[44]  J. Sherley,et al.  Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. , 2002, Cancer research.

[45]  Christopher S Potten,et al.  Intestinal stem cells protect their genome by selective segregation of template DNA strands. , 2002, Journal of cell science.

[46]  L. Mullenders,et al.  The role of nucleotide excision repair in protecting embryonic stem cells from genotoxic effects of UV-induced DNA damage. , 1999, Nucleic acids research.

[47]  T. Taguchi,et al.  Increased sister-chromatid exchanges (SCEs) and chromosomal fragilities by BrdU in a human mutant B-lymphoblastoid cell line. , 1989, Mutation research.

[48]  G. Schultz,et al.  Paternal DNA strands segregate to both trophectoderm and inner cell mass of the developing mouse embryo. , 1988, Genes & development.

[49]  J. McGhee,et al.  Parental DNA strands segregate randomly during embryonic development of Caenorhabditis elegans , 1987, Cell.

[50]  L. Gianni,et al.  Pharmacological evaluation of intravenous delivery of 5-bromodeoxyuridine to patients with brain tumors. , 1984, Cancer research.

[51]  R. Davidson,et al.  Resistance to bromodeoxyuridine mutagenesis and toxicity in mammalian cells selected for resistance to hydroxyurea , 1979, Somatic cell genetics.

[52]  J. Cairns,et al.  The segregation of DNA in epithelial stem cells , 1978, Cell.

[53]  John Cairns,et al.  Mutation selection and the natural history of cancer , 1975, Nature.

[54]  K. Lark,et al.  Segregation of Sister Chromatids in Mammalian Cells , 1966, Science.

[55]  W. Huttner,et al.  Nonselective sister chromatid segregation in mouse embryonic neocortical precursor cells. , 2009, Cerebral cortex.