Somatic cell-like features of cloned mouse embryos prepared with cultured myoblast nuclei

Shaorong Gao, Young Gie Chung, Jean W. Williams, Joan Riley, Kelle Moley, Keith E. Latham*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Cloning by somatic cell nuclear transfer requires silencing of the donor cell gene expression program and the initiation of the embryonic gene expression program (nuclear reprogramming). Failure to silence the donor cell program could lead to altered embryonic phenotypes. Cloned mouse embryos produced using myoblast nuclei fail to thrive in standard embryo culture media but flourish in somatic cell culture media favored by the donor myoblasts themselves, forming blastocysts at a significant rate, with robust morphologies, high total cell number, and a normal allocation of cells to the inner cell mass in most embryos. Myoblast cloned embryos continue expressing the GLUT4 glucose transporter, which is typically expressed in muscle but not in preimplantation stage embryos. Myoblast clones also exhibit precocious enrichment of GLUT1 at the cell surface. Both myoblast and cumulus cell cloned embryos exhibit enhanced rates of glucose uptake. These observations indicate that silencing of the donor cell genome during cloning either is incomplete or occurs progressively over the course of preimplantation development. As a result, cloned embryos initially exhibit many somatic cell-like characteristics. Tetraploid constructs, which possess a transplanted somatic cell genome plus the oocyte-derived chromosomes, exhibit a more embryonic-like pattern of gene expression and culture preference. We conclude that preimplantation stage cloned embryos have profoundly altered characteristics that are donor cell type specific and that exposure of cloned embryos to standard embryo culture conditions may lead to disruptions in basic homeostasis and inhibition of a range of essential processes including further nuclear reprogramming, contributing to cloned embryo demise.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalBiology of reproduction
Volume69
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Keywords

  • Developmental biology
  • Early development
  • Embryo
  • Gene regulation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Fingerprint

Dive into the research topics of 'Somatic cell-like features of cloned mouse embryos prepared with cultured myoblast nuclei'. Together they form a unique fingerprint.

Cite this