RT Journal Article
SR Electronic
T1 Trophectoderm Potency is Retained Exclusively in Human Naïve Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.04.933812
DO 10.1101/2020.02.04.933812
A1 Ge Guo
A1 Giuliano Giuseppe Stirparo
A1 Stanley Strawbridge
A1 Jian Yang
A1 James Clarke
A1 Meng Amy Li
A1 Sam Myers
A1 Buse Nurten Özel
A1 Jennifer Nichols
A1 Austin Smith
YR 2020
UL http://biorxiv.org/content/early/2020/02/04/2020.02.04.933812.abstract
AB Classical mouse embryology has established a sequence of lineage bifurcations underpinning early mammalian development. Consistent with this paradigm, mouse embryonic stem cells have lost the capacity to generate extraembryonic trophectoderm. We show here, however, that human naïve epiblast stem cells readily produce this lineage. Inhibition of ERK signalling, fundamental to naïve cell propagation, is unexpectedly instrumental in trophectoderm induction. Transcriptome analyses authenticate trophoblast fate and expose a trajectory via reversion to inner cell mass (ICM). Nodal inhibition enhances differentiation and BMP signalling is not engaged. Strikingly, after formative transition primed stem cells cannot make trophectoderm but respond to BMP and form amnion. Gene perturbations in naïve cells reveal that YAP and TFAP2C promote trophectoderm as in mouse, while NANOG suppresses distinctively in human. Finally, ICMs from expanded human blastocysts efficiently regenerate trophectoderm. Thus in human, retained trophectoderm potential is an integral feature of emergent pluripotency that confers higher regulative plasticity.