Abstract

Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.

Highlights

  • Generation of pluripotent stem cells (PSCs), including embryonic (ESCs) and induced PSCs, from cattle has been the most challenging of all mammalian species

  • This review will provide a summary of major efforts and advances in the pursuit of bovine PSCs

  • Using an interspecies chimera approach, human “naive” induced pluripotent stem cells (iPSCs) formed chimeras when injected into murine, porcine and bovine blastocysts[15] while primed human iPSCs failed to do so[16]

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Summary

Introduction

Generation of pluripotent stem cells (PSCs), including embryonic (ESCs) and induced PSCs, from cattle has been the most challenging of all mammalian species. The gold-standard mouse ESCs are capable of in vitro differentiation into embryoid bodies as well as in vivo differentiation into teratoma and formation of germline chimeras[4] It is unethical, to produce germline chimeras in humans, the demonstration of human pluripotency has had to stop at the stage of teratoma formation. The term, primed pluripotency[6], was coined to describe human ESCs and mouse epiblast stem cells[7,8]. The ultimate goal of naive human iPSCs has been eagerly pursued and recently reported[12,13,14] These cells exhibit more differentiation potential than their primed counterparts. Using an interspecies chimera approach, human “naive” iPSCs formed chimeras when injected into murine, porcine and bovine blastocysts[15] while primed human iPSCs failed to do so[16]

Current status of bovine ESCs and iPSCs
Attempts to produce bovine germline chimeras and pluripotency testing
Future directions of bovine PSCs research
Applications of bovine PSCs
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