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New intermediate stem cell type derived

7 December 2020
Appeared in BioNews 1075

Development of a new 'intermediate' embryonic stem cell type, able to generate gamete cells and chimeras, could lead to advances in regenerative medicine and reproductive biology.

Cells in early embryos have pluripotent properties, meaning that the cells are able to create various tissue types in the body. There are two distinct pluripotent states observed in embryonic stem cells from mice, which have been extensively studied: 'naïve' embryonic stem cells and 'primed' epiblast stem cells. However, there is a third state that exists between these two stages, which researchers have been unable to study as no method of maintaining these cells in their intermediate state has been determined.

Researchers, led by Dr Jun Wu at University of Texas Southwestern, Dallas, created intermediate pluripotent stem cells (PSCs), which they termed XPSCs. 'These XPSCs have enormous potential', explained Dr Wu. 'These results could eventually lead to an array of advances in both basic and applied research.'

XPSCs were derived from mouse, horse, and human cells, remaining stable in culture and multiplying without further development for approximately two years. The researchers did observe differences in pluripotency features across the three species, with horse XPSCs more closely resembling human than mouse.

The research team also successfully created intraspecies chimeras using mice from two breeds and interspecies chimeras using horse and mice.

The intraspecies mouse chimeras were created using cells derived from mice with different coat colours. Fluorescently labelled XPSCs contributed to different fetal tissues, generating cells from all three germ layers, and showed efficient germline transmission.

For the interspecies chimeras, horse XPSCs were injected into early mouse embryos. The scientists discovered that the horse XPSCs were able to contribute to chimera formation in mouse embryos with the development of mouse organs. Given the difference in horse and mouse gestation periods (approximately 11-12 months vs 20 days respectively) the authors suggested that donor cells were able to adapt to host developmental timing.

Further experiments in vitro have shown that XPSCs are able to differentiate into primordial germ cell-like cells, which are the precursors to eggs and sperm.

Published in Cell Stem Cell, Dr Wu concluded that 'Our study helps open the door to [many] possibilities.' By using chimera-derived primordial germ cells to create sperm and eggs, one such possibility that Dr Wu suggested is that this research could help in the advancement of infertility treatments.

Derivation of intermediate pluripotent stem cells amenable to primordial germ cell specification
Cell Stem Cell |  2 December 2020
Development of new stem cell type may lead to advances in regenerative medicine
UT Southwestern |  3 December 2020
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