Incomplete epigenetic reprogramming keeps cloning efficiency low, review finds

Somatic cell nuclear transfer (SCNT), the cloning technique that transfers a somatic cell genome into an egg cell and confers totipotency onto it, continues to promise major gains in animal germplasm conservation, livestock breeding and biomedical research. Yet according to a new review published in Epigenetics & Chromatin, mammalian cloning efficiency remains low and has seen little progress in recent years, and the authors attribute this to incomplete epigenetic reprogramming of the transferred genome.

It systematically outlines what the authors describe as the core and emerging epigenetic barriers in SCNT embryos, the obstacles that prevent a fully differentiated cell nucleus from being reset to an embryonic state capable of supporting normal development.

The low viability of cloned animals and the frequent developmental abnormalities observed in them are widely recognized, the authors write, to be attributable to this incomplete epigenetic reprogramming. When this remodeling is inefficient, development fails or produces abnormal offspring.

A central theme of the review is that recent technological advances, particularly low-input sequencing methods, have driven new breakthroughs in research aimed at improving cloning efficiency.

Beyond cataloguing barriers, the review provides what the authors call a comprehensive evaluation of the latest strategies to increase cloning efficiency.

The authors also address current challenges and future research directions in the field, offering what they describe as novel insights for studies and practices aimed at enhancing somatic cell cloning efficiency.

The article is published as a peer-reviewed, accepted manuscript shared ahead of the final Version of Record, a format the journal uses to provide faster access while the text undergoes further edits. It carries a permanent DOI and is citable in this form.

As a review article, the paper synthesizes existing literature rather than presenting new experimental results. Its conclusions reflect the state of the SCNT field as assessed by its authors: that epigenetic barriers remain the principal limitation on cloning success, and that precision approaches to epigenetic and genetic regulation represent the most promising route toward improving the efficiency of somatic cell cloning in mammals.

Subject of Research: Epigenetic barriers to efficient somatic cell nuclear transfer cloning and strategies to overcome them

Article Title: Epigenetic reprogramming in SCNT embryos: from inefficient remodeling to precision enhancement

Article References: Zhao, Y., Wang, Y., Wang, Y., Yu, S., Yang, H., Miao, M., Zhou, H., Sun, H., Sun, B., Bie, L., & Liang, S. (2026). Epigenetic reprogramming in SCNT embryos: from inefficient remodeling to precision enhancement. Epigenetics & Chromatin. https://doi.org/10.1186/s13072-026-00691-0

Image Credits: AI Generated

DOI: 10.1186/s13072-026-00691-0

Keywords: SCNT, cloning, epigenetic reprogramming, somatic cell nuclear transfer, DNA methylation, histone modifications, low-input sequencing, developmental abnormalities, livestock, germplasm conservation, Epigenetics & Chromatin, review