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Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation

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Abstract

The aim of this study was to determine whether the number of passages affected the developmental pluripotency of embryonic stem (ES) cells as measured by the attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid embryo complementation. Thirty-six newborns were produced by the aggregation of tetraploid embryos and hybrid ES cells after various numbers of passages. These newborns were entirely derived from ES cells as judged by microsatellite DNA, coat-color phenotype, and germline transmission. Although 15 survived to adulthood, 17 died of respiratory failure, and four were eaten by their foster mother. From the 15 mice that reached adulthood and that could reproduce, none arose from ES cells at passage level 15 or more. All 15 arose from cells at passages 3–11. Our results demonstrate that the number of passages affects the developmental pluripotency of ES cells.

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References

  • Boyd S (2004) Causes and treatment of neonatal respiratory distress syndrome. Nurs Times 100:40–44

    Google Scholar 

  • Brook FA, Gardner RL (1997) The origin and efficient derivation of embryonic stem cells in the mouse. Proc Natl Acad Sci USA 94:5709–5712

    Article  PubMed  CAS  Google Scholar 

  • Dean W, Bowden L, Aitchison A, Klose J, Moore T, Meneses JJ, Reik W, Feil R (1998) Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes. Development 125:2273–2282

    PubMed  CAS  Google Scholar 

  • Eakin GS, Behringer RR (2003) Tetraploid development in the mouse. Dev Dyn 228:751–766

    Article  PubMed  Google Scholar 

  • Eakin GS, Hadjantonakis AK, Papaioannou VE, Behringer RR (2005) Developmental potential and behavior of tetraploid cells in the mouse embryo. Dev Biol 288:150–159

    Article  PubMed  CAS  Google Scholar 

  • Eggan K, Jaenisch R (2003) Differentiation of F1 embryonic stem cells into viable male and female mice by tetraploid embryo complementation. Methods Enzymol 365:25–39

    Article  PubMed  Google Scholar 

  • Eggan K, Akutsu H, Loring J, Jackson-Grusby L, Klemm M, Rideout WM, Yanagimachi R, Jaenisch R (2001) Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci USA 98:6209–6214

    Article  PubMed  CAS  Google Scholar 

  • Eggan K, Rode A, Jentsch I, Samuel C, Hennek T, Tintrup H, Zevnik B, Erwin J, Loring J, Jackson-Grusby L, Speicher MR, Kuehn R, Jaenisch R (2002) Male and female mice derived from the same embryonic stem cell clone by tetraploid embryo complementation. Nat Biotechnol 20:455–459

    Article  PubMed  CAS  Google Scholar 

  • Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R (2004) Mice cloned from olfactory sensory neurons. Nature 428:44–49

    Article  PubMed  CAS  Google Scholar 

  • Hochedlinger K, Jaenisch R (2002) Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 415:1035–1038

    Article  PubMed  CAS  Google Scholar 

  • Humpherys D, Eggan K, Akutsu H, Hochedlinger K, Rideout WM 3rd, Biniszkiewicz D, Yanagimachi R, Jaenisch R (2001) Epigenetic instability in ES cells and cloned mice. Science 293:95–97

    Article  PubMed  CAS  Google Scholar 

  • James RM, Kaufman MH, Webb S, West JD (1992) Electrofusion of mouse embryos results in uniform tetraploidy and not tetraploid/diploid mosaicism. Genet Res 60:185–194

    Article  PubMed  CAS  Google Scholar 

  • Kaufman MH, Webb S (1990) Postimplantation development of tetraploid mouse embryos produced by electrofusion. Development 110:1121–1132

    PubMed  CAS  Google Scholar 

  • Li X, Yu Y, Wei W, Yong J, Yang J, You J, Xiong X, Qing T, Deng H (2005a) Simple and efficient production of mice derived from embryonic stem cells aggregated with tetraploid embryos. Mol Reprod Dev 71:154–158

    Article  PubMed  CAS  Google Scholar 

  • Li X, Wei W, Yong J, Jia Q, Yu Y, Di K (2005b) The genetic heterozygosity and fitness of tetraploid embryos and embryonic stem cells are crucial parameters influencing survival of mice derived from embryonic stem cells by tetraploid embryo aggregation. Reproduction 130:53–59

    Article  PubMed  CAS  Google Scholar 

  • Mann MR, Chung YG, Nolen LD, Verona RI, Latham KE, Bartolomei MS (2003) Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos. Biol Reprod 69:902–914

    Article  PubMed  CAS  Google Scholar 

  • McWhir J, Schnieke AE, Ansell R, Wallace H, Colman A, Scott AR, Kind AJ (1996) Selective ablation of differentiated cells permits isolation of embryonic stem cell lines from murine embryos with a non-permissive genetic background. Nat Genet 14:223–226

    Article  PubMed  CAS  Google Scholar 

  • Nagy A, Gocza E, Diaz EM, Prideaux V, Ivçnyi E, Markkula M, Rossant J (1990) Embryonic stem cells alone are able to support fetal development in the mouse. Development 110:815–821

    PubMed  CAS  Google Scholar 

  • Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder JC (1993) Derivation of completely cell culture-derived mice from early-passage embryonic stem cells. Proc Natl Acad Sci USA 90:8424–8428

    Article  PubMed  CAS  Google Scholar 

  • Nagy A, Gertsenstein M, Vintersten K, Behringer R (2003) Manipulating the mouse embryo: a laboratory manual. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, New York, pp 453–506

    Google Scholar 

  • O’Shea KS (2004) Self-renewal vs. differentiation of mouse embryonic stem cells. Biol Reprod 71:1755–1765

    Article  PubMed  CAS  Google Scholar 

  • Rachel E, Nissim B (2002) A molecular view on pluripotent stem cells. FEBS Lett 529:135–141

    Article  Google Scholar 

  • Rie S, Aya S, Michiko H, Akio T, Hiroyoshi I, Ying L, Satoshi K, Fumihiro S, Ken-ichi Y (2005) Establishment of a new embryonic stem cell line derived from C57BL/6 mouse expressing EGFP ubiquitously. Genesis 42:47–52

    Article  CAS  Google Scholar 

  • Schalkwyk LC, Jung M, Daser A, Weiher M, Walter J, Himmelbauer H, Lehrach H (1999) Panel of microsatellite markers for whole-genome scans and radiation hybrid mapping and a mouse family tree. Genome Res 9:878–887

    Article  PubMed  CAS  Google Scholar 

  • Shiue YL, Liou JF, Shiau JW, Yang JR, Chen YH, Tailiu JJ, Chen LR (2006) In vitro culture period but not the passage number influences the capacity of chimera production of inner cell mass and its deriving cells from porcine embryos.Anim Reprod Sci 93:134–143

    Article  PubMed  Google Scholar 

  • Schumacher A, Doerfler W (2004) Influence of in vitro manipulation on the stability of methylation patterns in the Snurf/Snrpn-imprinting region in mouse embryonic stem cells. Nucleic Acids Res 32:1566–1576

    Article  PubMed  CAS  Google Scholar 

  • Schwenk F, Zevnik B, Bruning J, Rohl M, Willuweit A, Rode A, Hennek T, Kauselmann G, Jaenisch R, Kuhn R (2003) Hybrid embryonic stem cell-derived tetraploid mice show apparently normal morphological, physiological, and neurological characteristics. Mol Cell Biol 23:3982–3989

    Article  PubMed  CAS  Google Scholar 

  • Seibler J, Zevnik B, Küter-Luks B, Andreas S, Kern H, Hennek T, Rode A, Heimann C, Faust N, Kauselmann G, Schoor M, Jaenisch R, Rajewsky K, Kühn R, Schwenk F (2003) Rapid generation of inducible mouse mutants. Nucleic Acids Res 31:e12

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Jaenisch R (2004) At most three ES cells contribute to the somatic lineages of chimeric mice and of mice produced by ES-tetraploid complementation. Dev Biol 275:192–201

    Article  PubMed  CAS  Google Scholar 

  • Wang ZQ, Kiefer F, Urbanek P, Wagner EF (1997) Generation of completely embryonic stem cell-derived mutant mice using tetraploid blastocyst injection. Mech Dev 62:137–145

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Ren J, Ryan T, Higgins P, Tim M (2004) Rapid tagging of endogenous mouse genes by recombineering and ES cell complementation of tetraploid blastocysts. Nucleic Acids Res 32:e128

    Article  PubMed  CAS  Google Scholar 

  • Zvetkova I, Apedaile A, Ramsahoye B, Mermoud JE, Crompton LA, John R, Feil R, Brockdorff N (2005) Global hypomethylation of the genome in XX embryonic stem cells. Nat Genet 37:1274–1279

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We are grateful to Mrs. Jie Fang You and Mrs. Xiao Ran Xiong for culturing the ES cells used in our studies, to Ya Shu Liu for PCR primer pairs, and to Dr. Jie Yang for microsatellite DNA analysis.

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Correspondence to Xiang-yun Li.

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This work was supported by the National Natural Science Foundation of China (grant no. 30571336) and the President Foundation of the Agricultural University of Hebei.

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Li, Xy., Jia, Q., Di, Kq. et al. Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation. Cell Tissue Res 327, 607–614 (2007). https://doi.org/10.1007/s00441-006-0354-6

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  • DOI: https://doi.org/10.1007/s00441-006-0354-6

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