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Pluripotency deficit in clones overcome by clone-clone aggregation: epigenetic complementation?

Michele Boiani1, Sigrid Eckardt, N Adrian Leu

  • 1Germline Development Group, Center for Animal Transgenesis and Germ Cell Research, New Bolton Center, University of Pennsylvania, Kennett Square, PA 19348, USA.

The EMBO Journal
|October 1, 2003
PubMed

Insights

Somatic cell cloning errors cause abnormal gene expression. Aggregating genetically identical clones improved Oct4 expression and development, suggesting epigenetic complementation, not just cell number, corrects defects.

Area of Science:

  • Developmental Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Somatic cell cloning often results in abnormal gene expression and developmental issues.
  • Errors in nuclear reprogramming are typically blamed for these cloning defects.
  • Oct4 gene expression is critical for early embryonic development and pluripotency.

Purpose of the Study:

  • To investigate the cause of abnormal gene expression in cloned embryos.
  • To determine if increasing cell number in cloned embryos improves development.
  • To explore the role of epigenetic complementation in cloned embryo development.

Main Methods:

  • Created mouse somatic cell clones and aggregated them at the 4-cell stage.
  • Assessed blastocyst cell number and Oct4 gene expression.
  • Compared development of clone-clone aggregates with control blastocysts and manipulated low-cell-number blastocysts.

Main Results:

  • Mouse clone blastocysts had significantly fewer cells than normal.
  • Aggregating genetically identical clones improved Oct4 expression and increased fetal/postnatal development rates.
  • Low cell number alone did not cause abnormal Oct4 expression in non-cloned embryos.

Conclusions:

  • Improved gene expression and development in clone-clone aggregates stem from epigenetic complementation, not solely increased cell number.
  • Genetically identical but epigenetically distinct embryos can correct non-cell-autonomous defects upon aggregation.
  • This study offers new insights into overcoming developmental barriers in somatic cell cloning.

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