STAT3 Signalling Enhances Tissue Expansion During Postimplantation Mouse Development

STAT3 signalling has been studied extensively in the context of self-renewal and differentiation of mouse embryonic stem cells. Zygotic STAT3 is required for normal postimplantation development. On an outbred genetic background, Stat3 null embryos consistently lagged behind their littermates, beginning with significant reduction of epiblast cells at implantation. Remarkably, mutants closely resemble non-affected embryos from the previous day at all postimplantation stages examined. We pinpoint this phenotype to loss of the serine-phosphorylated form of STAT3 which predominates in postimplantation embryonic tissues. Bulk RNA-sequencing analysis of isolated mouse epiblasts confirmed Stat3 null embryos exhibited developmental delay transcriptionally. Single cell RNA sequencing of mid gestation chimaeras containing STAT3 null embryonic stem cells revealed exclusion of mutant cells exclusively from the erythroid lineage. Although Stat3 null embryonic stem cells can differentiate into erythroid and hematopoietic lineages in vitro, they are out-competed when mixed with wild type cells. Combined with the reduced size of STAT3 null epiblasts after implantation, our results implicate a role for STAT3 in cell proliferation affecting temporal control of embryonic progression and rapid differentiation.