In vitro generation of mouse morula-like cells.

Generating cells with the molecular and functional properties of embryo cells and with full developmental potential is an aim with fundamental biological significance. Here we report the in vitro generation of mouse transient morula-like cells (MLCs) via the manipulation of signaling pathways. MLCs are molecularly distinct from embryonic stem cells (ESCs) and cluster instead with embryo 8- to 16-cell stage cells. A single MLC can generate a blastoid, and the efficiency increases to 80% when 8–10 MLCs are used. MLCs make embryoids directly, efficiently, and within 4 days. Transcriptomic analysis shows that day 4–5 MLC-derived embryoids contain the cell types found in natural embryos at early gastrulation. Furthermore, MLCs introduced into morulae segregate into epiblast (EPI), primitive endoderm (PrE), and trophectoderm (TE) fates in blastocyst chimeras and have a molecular signature indistinguishable from that of host embryo cells. These findings represent the generation of cells that are molecularly and functionally similar to the precursors of the first three cell lineages of the embryo. [Display omitted] • Stat3 activation induces the generation of transient morula-like cells (MLCs) • MLCs segregate rapidly into cells representing the first three embryo lineages • MLCs make embryoids directly and reach an early gastrulation-like stage within 4 days • MLCs have in vitro and in vivo embryonic and extraembryonic developmental potential Li et al. report that increased Stat3 activation reprograms mouse embryonic stem cells into cells with molecular and functional properties of morula. Such morula-like cells have in vitro and in vivo embryonic and extraembryonic developmental competence, suggesting that such cells may be precursor cells of the first three embryo lineages. [ABSTRACT FROM AUTHOR]