Birth of Parthenote Mice Directly from Parthenogenetic Embryonic Stem Cells

Authors


  • Author contributions: L.L.: conception and design, financial support, final approval of manuscript; Z.C.: collection and assembly of data, data analysis and interpretation, manuscript writing; J.H.: collection and assembly of data, data analysis and interpretation; Z.L., C.L., B.L., C.W., S.C., T.A.: collection and assembly of data; L.Z.: provision of study material; M.G.C.: collection and assembly of data, data analysis and interpretation; D.L.K., X.Y., data analysis and interpretation, financial support, final approval of manuscript.

  • First published online in STEM CELLS EXPRESS June 19, 2009.

Abstract

Mammalian parthenogenetic embryos are not viable and die because of defects in placental development and genomic imprinting. Parthenogenetic ESCs (pESCs) derived from parthenogenetic embryos might advance regenerative medicine by avoiding immuno-rejection. However, previous reports suggest that pESCs may fail to differentiate and contribute to some organs in chimeras, including muscle and pancreas, and it remains unclear whether pESCs themselves can form all tissue types in the body. We found that derivation of pESCs is more efficient than of ESCs derived from fertilized embryos, in association with reduced mitogen-activated protein kinase signaling in parthenogenetic embryos and their inner cell mass outgrowth. Furthermore, in vitro culture modifies the expression of imprinted genes in pESCs, and these cells, being functionally indistinguishable from fertilized embryo-derived ESCs, can contribute to all organs in chimeras. Even more surprisingly, our study shows that live parthenote pups were produced from pESCs through tetraploid embryo complementation, which contributes to placenta development. This is the first demonstration that pESCs are capable of full-term development and can differentiate into all cell types and functional organs in the body. STEM CELLS 2009;27:2136–2145

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