Myc is required for early embryo development

Myc is required for early embryo development

The Myc family of transcription factors comprises c-Myc, N-Myc, and L-Myc and has been implicated in the generation of a variety of human tumors.  The role of Myc proteins in development has been widely investigated making use of gene targeting in mice: whereas L-myc knockout mice develop normally, embryos lacking c-myc die before E10.5 due to hematopoietic and placental defects, and N-myc-deficient embryos die before E11.5 displaying neuroectodermal and heart defects.

Myc activity is essential for efficient cellular reprogramming and has complex roles in various stem and progenitor cell types. The precise function of Myc in naive groundstate ESCs and the role of Myc in the mouse epiblast remain elusive

Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors.

Researchers show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest.

This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause.

Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKOESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients.

This study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.