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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: 2021-02-16
    Description: The production of blood cells during steady-state and increased demand depends on the regulation of hematopoietic stem cell (HSC) self-renewal and differentiation. Similarly, the balance between self-renewal and differentiation of leukemia stem cells (LSCs) is crucial in the pathogenesis of leukemia. Here, we document that the TNF receptor superfamily member lymphotoxin-β receptor (LTβR) and its ligand LIGHT regulate quiescence and self-renewal of murine and human HSCs and LSCs. Cell-autonomous LIGHT/LTβR signaling on HSCs reduces cell cycling, promotes symmetric cell division and prevents primitive HSCs from exhaustion in serial re-transplantation experiments and genotoxic stress. LTβR deficiency reduces the numbers of LSCs and prolongs survival in a murine chronic myeloid leukemia (CML) model. Similarly, LIGHT/LTβR signaling in human G-CSF mobilized HSCs and human LSCs results in increased colony forming capacity in vitro. Thus, our results define LIGHT/LTβR signaling as an important pathway in the regulation of the self-renewal of HSCs and LSCs.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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