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Updated: Apr 19, 2026
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RNA-based Reprogramming of Human Primary Fibroblasts into Induced Pluripotent Stem Cells
Published on: November 26, 2018
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Ovine induced pluripotent stem cells are resistant to reprogramming after nuclear transfer
Sergio D German1, Keith H S Campbell, Elisabeth Thornton
11 Division of Animal Sciences, School of Biosciences, University of Nottingham , Loughborough, LE12 5RD, United Kingdom .
Cellular Reprogramming
|December 17, 2014
Summary
Induced pluripotent stem cells (iPSCs) from sheep could not successfully generate cloned farm animals. Persistent transgene expression and chromosomal abnormalities in iPSCs hindered normal embryonic development after nuclear transfer.
Area of Science:
- Reproductive biology and stem cell research in agriculture.
Background:
- Embryonic stem cells (ESCs) are not derivable from farm animals, limiting genetic modification via nuclear transfer (NT).
- Induced pluripotent stem cells (iPSCs) offer potential as ESC substitutes for creating genetically modified cloned farm animals.
Purpose of the Study:
- To evaluate the suitability of ovine iPSCs as a substitute for ESCs in generating genetically modified cloned farm animals through NT.
Main Methods:
- Ovine iPSCs were generated using retroviral transduction of the four Yamanaka factors.
- iPSCs were synchronized to G1 phase before nuclear transfer (NT) into enucleated oocytes.
- Embryonic development and gene expression in resulting blastocysts were analyzed.
Main Results:
- Ovine iPSCs exhibited bFGF- and activin A-dependency, persistent transgene expression, and chromosomal abnormalities.
- iPSC-NT embryos showed significantly lower blastocyst development rates (2%) compared to somatic cell NT (10%).
- Blastocysts from iPSC-NT displayed persistent transgenes, aberrant SOX2 expression, and failed NANOG activation.
Conclusions:
- Persistent exogenous factor expression and chromosomal abnormalities in iPSCs are detrimental to normal development of NT embryos.
- Ovine iPSCs are currently unsuitable for generating genetically modified cloned farm animals via NT.
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