Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1976 Feb; 73(2): 549–553.
PMCID: PMC335947

Totipotency and normal differentiation of single teratocarcinoma cells cloned by injection into blastocysts.


A definitive test for developmental totipotency of mouse malignant teratocarcinoma cells was conducted by cloning singly injected cells in genetically marked blastocysts. Totipotency was conclusively shown in an adult mosaic female whose tumor-strain cells had made substantial contributions to all of the wide range of its somatic tissues analyzed; the clonally propagated cell lineage had therefore differentiated in numerous normal directions. The test cells were from "cores" of embryoid bodies of a euploid, chromosomally male (X/Y), ascites tumor grown only in vivo by transplantation for 8 years. The capacity of cells from the same source to differentiate, in a phenotypic male, into reproductively functional sperms, has been shown in our previous experiments [(1975) Proc. Nat. Acad. Sci. USA 72, 3585-3589]. Cells from this transplant line therefore provide material suitable for projected somatic and germ-line genetic analyses of mammalian differentiation based on "cycling" of mutation-carrying tumor cells through developing embryos. In some animals obtained from single-cell injections tumor-derived cells were sporadically distributed in developmentally unrelated tissues. These cases can be accounted for by delayed and haphazard cellular integration, and by a marked degree of sustained cellular developmental flexibility in early mammalian development, irrespective of certain classical "germ-layer" designations. All mosaic mice obtained have thus far been free of teratomas. In one case, the injected stem cell contributed only to the pancreas and gave rise to a malignancy resembling pancreatic adenocarcinoma. The high modal frequency of euploidy in these individually tested cells thus tends to indicate that a near-normal chromosome complement is sufficient for total restoration of orderly gene expression in a normal embryonic environment; it may also be necessary for teratoma stem-cell proliferation to be terminated there.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Papaioannou VE, McBurney MW, Gardner RL, Evans MJ. Fate of teratocarcinoma cells injected into early mouse embryos. Nature. 1975 Nov 6;258(5530):70–73. [PubMed]
  • Stevens LC. The biology of teratomas. Adv Morphog. 1967;6:1–31. [PubMed]
  • STEVENS LC, HUMMEL KP. A description of spontaneous congenital testicular teratomas in strain 129 mice. J Natl Cancer Inst. 1957 May;18(5):719–747. [PubMed]
  • Mintz B, Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585–3589. [PMC free article] [PubMed]
  • Dunn GR, Stevens LC. Determination of sex of teratomas derived from early mouse embryos. J Natl Cancer Inst. 1970 Jan;44(1):99–105. [PubMed]
  • Lin TP. Microinjection of mouse eggs. Science. 1966 Jan 21;151(3708):333–337. [PubMed]
  • Gearhart JD, Mintz B. Clonal origins of somites and their muscle derivatives: evidence from allophenic mice. Dev Biol. 1972 Sep;29(1):27–37. [PubMed]
  • Mintz B, Baker WW. Normal mammalian muscle differentiation and gene control of isocitrate dehydrogenase synthesis. Proc Natl Acad Sci U S A. 1967 Aug;58(2):592–598. [PMC free article] [PubMed]
  • Snell GD, Graff RJ, Cherry M. Histocompatibility genes of mice. XI. Evidence establishing a new histocompatibility locus, H-12, and new H-2 allele, H-2bc. Transplantation. 1971 Jun;11(6):525–530. [PubMed]
  • Mintz B. Gene control of mammalian differentiation. Annu Rev Genet. 1974;8:411–470. [PubMed]
  • Mintz B. Gene control of mammalian pigmentary differentiation. I. Clonal origin of melanocytes. Proc Natl Acad Sci U S A. 1967 Jul;58(1):344–351. [PMC free article] [PubMed]
  • Brinster RL. The effect of cells transferred into the mouse blastocyst on subsequent development. J Exp Med. 1974 Oct 1;140(4):1049–1056. [PMC free article] [PubMed]
  • Damjanov I, Solter D, Belicza M, Skreb N. Teratomas obtained through extrauterine growth of seven-day mouse embryos. J Natl Cancer Inst. 1971 Mar;46(3):471–passim. [PubMed]
  • Damjanov I, Solter D, Skreb N. Enzyme histochemistry of experimental embryo-derived teratocarcinomas. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1971;76(4):249–256. [PubMed]
  • Levak-Svajger B, Svajger A. Investigation on the origin of the definitive endoderm in the rat embryo. J Embryol Exp Morphol. 1974 Oct;32(2):445–459. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    NCBI Bookshelf books that cite the current articles.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...