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  • 1
    Publication Date: 2000-04-28
    Description: The potential of cloning depends in part on whether the procedure can reverse cellular aging and restore somatic cells to a phenotypically youthful state. Here, we report the birth of six healthy cloned calves derived from populations of senescent donor somatic cells. Nuclear transfer extended the replicative life-span of senescent cells (zero to four population doublings remaining) to greater than 90 population doublings. Early population doubling level complementary DNA-1 (EPC-1, an age-dependent gene) expression in cells from the cloned animals was 3.5- to 5-fold higher than that in cells from age-matched (5 to 10 months old) controls. Southern blot and flow cytometric analyses indicated that the telomeres were also extended beyond those of newborn (〈2 weeks old) and age-matched control animals. The ability to regenerate animals and cells may have important implications for medicine and the study of mammalian aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lanza, R P -- Cibelli, J B -- Blackwell, C -- Cristofalo, V J -- Francis, M K -- Baerlocher, G M -- Mak, J -- Schertzer, M -- Chavez, E A -- Sawyer, N -- Lansdorp, P M -- West, M D -- AG00378/AG/NIA NIH HHS/ -- AI29524/AI/NIAID NIH HHS/ -- GM56162/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):665-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Advanced Cell Technology, One Innovation Drive, Worcester, MA 01605, USA. rlanza@advancedcell.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10784448" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blotting, Southern ; Cattle/*genetics ; *Cell Aging ; Cell Division ; Cells, Cultured ; Clone Cells ; *Cloning, Organism ; DNA, Complementary ; Embryo Transfer ; *Eye Proteins ; Female ; Fibroblasts ; Flow Cytometry ; In Situ Hybridization, Fluorescence ; Longevity ; Matched-Pair Analysis ; *Nerve Growth Factors ; *Nuclear Transfer Techniques ; Proteins/genetics ; RNA, Messenger/genetics/metabolism ; Serpins/genetics ; Telomere/*ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-12-18
    Description: It is generally assumed that sister chromatids are genetically and functionally identical and that segregation to daughter cells is a random process. However, functional differences between sister chromatids regulate daughter cell fate in yeast and sister chromatid segregation is not random in Escherichia coli. Differentiated sister chromatids, coupled with non-random segregation, have been proposed to regulate cell fate during the development of multicellular organisms. This hypothesis has not been tested because molecular features to reliably distinguish between sister chromatids are not obvious. Here we show that parental 'Watson' and 'Crick' DNA template strands can be identified in sister chromatids of murine metaphase chromosomes using CO-FISH (chromosome orientation fluorescence in situ hybridization) with unidirectional probes specific for centromeric and telomeric repeats. All chromosomes were found to have a uniform orientation with the 5' end of the short arm on the same strand as T-rich major satellite repeats. The invariable orientation of repetitive DNA was used to differentially label sister chromatids and directly study mitotic segregation patterns in different cell types. Whereas sister chromatids appeared to be randomly distributed between daughter cells in cultured lung fibroblasts and embryonic stem cells, significant non-random sister chromatid segregation was observed in a subset of colon crypt epithelial cells, including cells outside positions reported for colon stem cells. Our results establish that DNA template sequences can be used to distinguish sister chromatids and follow their mitotic segregation in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757939/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757939/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Falconer, Ester -- Chavez, Elizabeth A -- Henderson, Alexander -- Poon, Steven S S -- McKinney, Steven -- Brown, Lindsay -- Huntsman, David G -- Lansdorp, Peter M -- R01 GM094146/GM/NIGMS NIH HHS/ -- RMF-92093/Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Jan 7;463(7277):93-7. doi: 10.1038/nature08644. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Terry Fox Laboratory, B.C. Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016487" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chromatids/*genetics/*metabolism ; Chromosome Segregation/*physiology ; Colon/cytology ; DNA, Satellite/metabolism ; Embryonic Stem Cells/cytology ; Epithelial Cells/cytology ; Fibroblasts/cytology ; Fluorescence ; In Situ Hybridization, Fluorescence/*methods ; Luminescent Measurements ; Lung/cytology ; Mice ; Mice, Inbred C57BL ; Mitosis ; Models, Biological ; Organ Specificity ; Substrate Specificity ; Telomere/metabolism ; Templates, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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