RT Journal Article
SR Electronic
T1 Primate naïve pluripotent stem cells stall in the G1 phase of the cell cycle and differentiate prematurely during embryo colonization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.27.011890
DO 10.1101/2020.03.27.011890
A1 Irène Aksoy
A1 Cloé Rognard
A1 Anaïs Moulin
A1 Guillaume Marcy
A1 Etienne Masfaraud
A1 Florence Wianny
A1 Véronique Cortay
A1 Angèle Bellemin-Ménard
A1 Nathalie Doerflinger
A1 Manon Dirheimer
A1 Chloé Mayère
A1 Cian Lynch
A1 Olivier Raineteau
A1 Thierry Joly
A1 Colette Dehay
A1 Manuel Serrano
A1 Marielle Afanassieff
A1 Pierre Savatier
YR 2020
UL http://biorxiv.org/content/early/2020/03/28/2020.03.27.011890.abstract
AB After reprogramming to naïve pluripotency, human pluripotent stem cells (PSCs) still exhibit very low ability to make interspecies chimeras in mice and pigs. Whether this is because they are inherently devoid of the attributes of chimeric competency or because naïve PSCs in general cannot colonize embryos from distant species remains to be elucidated. Here, we have used different types of mouse, human and rhesus monkey naïve PSCs and we have analyzed their ability to colonize both distant (rabbit) and close (cynomolgus monkey) embryos. Mouse embryonic stem cells (ESCs) remained mitotically active after injection into rabbit and cynomolgus embryos and contributed to the formation of the neural tube in post-implantation rabbit embryos. In contrast, primate naive PSCs colonized rabbit and cynomolgus embryos with much lower efficiency, regardless of the reprogramming protocols. Unlike mouse ESCs, they slowed DNA replication following colony dissociation and, after injection into host embryos, they stalled in the G1 phase of the cell cycle and differentiated prematurely, regardless of host species, distant or close. These results show that, unlike mouse ESCs, primate naive PSCs do not make chimeras because they are inherently unfit to stay mitotically active during embryo colonization.