UNRESTRICTED LINEAGE DIFFERENTIATION OF PARTHENOGENETIC ES CELLS

The developmental potential of parthenogenetic embryonic stem (P-ES) c ells was studied in teratomas and mouse chimaeras. Teratomas derived f rom P-ES cells contained a mixture of tissue types with variable propo rtions of specific tissues. Three of the eight P-ES cell lines analyse d showed high proportions of striated muscle in teratomas, similar to teratomas from normal embryos or ES cell lines derived from fertilised embryos (F-ES cells). Our study also revealed that one P-ES cell line showed little lineage restriction in injection chimaeras. Descendants of the P-ES cells contributed to most tissues of chimaeric fetuses in patterns similar to F-ES cells. Normal colonisation of muscle, liver and pancreas was found in adult chimaeras. P-ES cells also showed simi lar haematopoietic differentiation and maturation as F-ES cells. Howev er, extensive P-ES cell contribution was associated with a reduction i n body size. These findings suggest that, while P-ES cells display mor e extensive developmental potential than the cells of parthenogenetic embryos from which they were derived, they only retained properties re lated to the presence of the maternal genome. To elucidate the molecul ar basis for the lack of lineage restriction during in vivo differenti ation, the expression of four imprinted genes, H19, Igf2r, Igf2 and Sn rpn was compared among five P-ES and two F-ES cell lines. Expression l evels of these genes varied among the different ES cell lines, both in undifferentiated ES cells and in embryoid bodies.