Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency

Abstract

SUMMARY Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research.

Interspecies chimeras for human stem cell research

“…However, whether the cells might show an even higher rate of chimerism with porcine embryos was not tested. It has also been shown that human PSC-derived cells in interspecies chimeras can differentiate into multiple lineages (Mascetti and Pedersen, 2016;Wu et al, 2015Wu et al, , 2017Yang et al, 2017), but whether their differentiation was autonomous or due to cooperative morphogenesis with host tissue is controversial. It remains to be seen whether organs and tissues can be cooperatively formed between host cells and transplanted human cells in these interspecies chimeras.…”

“…These results highlight the importance of genetic/evolutionary distance when generating interspecies chimeras. Interestingly, Yang et al (2017) recently reported that newly established human PSCs with an expanded developmental potential showed an improved rate of chimerism with mouse embryos. However, whether the cells might show an even higher rate of chimerism with porcine embryos was not tested.…”

357 Occupational exposure to selenium compounds, its effect on biological parameters and markers of diabetes

“…The field of stem cell embryology is in its infancy and will expand by tuning chemical and physical parameters, and using stem cell lines with broader developmental potential (64,65). Particularly interesting would be the combination of hESCs with human TSCs (66), and potentially human hypoblast stem cells, to recapitulate the human conceptus.…”

“…The derivation of extraembryonic stem cells that better match the expression signatures of real embryos should improve the morphology of these embryo-like structures (62,63). Similarly, the recent generation of expanded potential stem cells, which have the ability to form both embryonic and extraembryonic tissues, represents a promising tool for future research (64,65) …”

Porcine pluripotent stem cells: progress, challenges and prospects

“…To a certain extent, the biological characteristics of ESCs depend on culture conditions. The conversion of mouse EpiSCs into ESCs in 2i/LIF culture system and the conversion of mouse ESCs to expanded PSCs (EPSC), or vice versa, provides clear evidence for the importance of culture conditions [19][20][21][22] . Compared to the large number of studies examining appropriate culture conditions for mouse and human ESCs, minimal data are available for ESCs culture conditions of domestic animals [23] .…”