Abstract
Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eight-cell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.
Highlights
Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research
Under porcine EPSC medium (pEPSCM), bovine induced plurpotent stem cells (iPSCs) were eventually differentiated in longterm culturing, accompanied with down-regulation of core pluripotency genes and expression of both embryonic and extraembryonic cell-lineage genes, with differentiated cell morphology (Fig. 1 F and G and SI Appendix, Fig. S1A), demanding further adjustment of pEPSCM for bovine stem cells. pEPSCM contains inhibitors targeting GSK3, SRC, and Tanykrases [9]
In vitro and in teratomas, bovine iPSCs could differentiate into cells representative of both embryonic and extraembryonic cell-lineage genes (SI Appendix, Fig. S1 E–G) and were named as bEPSCiPS
Summary
Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. EPSCs are molecularly and functionally similar across species They possess robust selfrenewal capacity in long-term culture, allow efficient genome editing, and generate both embryonic and extraembryonic cell lineages in vitro and in chimeras in terms of mouse and porcine EPSCs [7,8,9]. BEPSCs express high levels of pluripotency genes, propagate robustly in single cell passaging, are genetically stable, and permit efficient precise gene editing They differentiate in vitro and in chimeras to both the embryonic and extraembryonic cell lineages. The availability of bEPSCs, which are robustness in culture, permit efficient genome editing, possess expanded developmental potential, are expected to substantially advance bovine stem cell biology to considerably facilitate selecting for superior animals for farming and to open up opportunities for biotechnology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
