Non-cell-autonomous control of gastruloid development by the lncRNA T-UCstem1 2 through DKK1-dependent modulation of WNT signalling

Here we use mouse gastruloids to investigate the role of an ultraconserved lncRNA, T-UCstem1, in the formation of the mammalian body plan using single cells transcriptomics, we provide unprecedented evidence that T-UCstem1 is a key regulator of gastruloid development and is required for the correct specification of the anterior-posterior axis. Specifically, knock down of T-UCstem1 results in aberrant gastruloid development, which is characterized by altered spatiotemporal expression of the differentiation markers and persistence of pluripotency genes. Single cell analysis reveals higher cellular heterogeneity in T-UCstem1 KD gastruloids. Notably, the presence of cell populations characterized by the co-expression of pluripotency and differentiation markers points to a key role of T-UCstem1 in establishment and maintenance of proper cellular identity.