Thanks Mo!😁

Thanks Srishti! 😁

Thanks Ekjot!😁

Tl;dr, MERVL is an integrator of multiple TFs to drive the 2C-like state, and drives some yet not all totipotency features. In contrast Dux-dependent toxicity is MERVL-independent and involves Noxa-induced apoptosis. Big thanks to all involved! @BryonyLeeke @Less_Sepulveda (8/8)

Noxa KO in ESCs reduces Dux-dependent apoptosis and is even upregulated in the muscular dystrophy, FSHD, which is driven by DUX4 mis-expression. It’ll be interesting in future to look at therapeutic NOXA reduction in FSHD myoblasts. (7/8)

What about cell death? Maintained expression of Dux causes toxicity in many cell types, and 2C arrest in embryos. We find Dux-driven toxicity to be MERVL independent, and identify Noxa as a Dux-specific target contributing to apoptosis. (6/8)

Yet: MERVL-induced 2C-like cells have the same expanded fate potential as Dux/control 2C-like cells. This means a core set of MERVL-dependent genes is enough for this totipotency feature. Also, only MERVL-dependent genes are downregulated upon OBOX loss, a new ZGA factor (5/8)

2C-like cells are not created equal! Dux-induced 2C-like cells mimic endogenous 2C-like cells, but MERVL-driven 2C-like cells are intermediate at gene and TE level. They also only show partial chromocentre loss and pluripotency factor downregulation (4/8)

We first established a CRISPRa system in a MERVL-GFP-CD4 reported cell line in order to specifically activate Dux or MERVL elements in order to assess MERVL contribution to the 2C transcriptome and repeatome. (3/8)

2C-like cells model 2-cell mouse embryos and express the TE MERVL, its potent activators such as Dux and OBOX. MERVL is essential in vivo, but not Dux. So what is needed for 2C-like features, and how are they driven? Also, Dux induces cell death – is this MERVL dependent? (2/8)

Happy to share our latest #preprint showcasing the work done during my postdoc in the lab of @MPercharde at the @MRC_LMS. We used CRISPRa to disentangle the close relationship between Dux and MERVL elements in the induction of the 2-cell like state. biorxiv.org/content/10.1101/… (1/8)

Congrats Cèsar!🥳

Congrats!🥳 enjoy your holidays😁

Congrats Julia! 🥳 looking forward to see you all do amazing things!