Regulation of mRNA polyadenylation governs mammalian body plan formation in gastruloids
Taborsky, D.; Valdivia-Francia, F.; Ranjbar, N.; Llop-Grau, L.; Dure, C.; Ghoshdastider, U.; Renz, P. F.; Weber, R.; Yigit, M.; Mironov, A.; Hyams, K.; Vianello, S.; Zavolan, M.; Lutolf, M. P.; Sendoel, A.
Show abstract
The establishment of the body plan during gastrulation represents a hallmark of animal life. It emerges from the interplay of gene-regulatory programs and positional cues, yet how these signals are integrated post-transcriptionally remains largely unexplored. Here, we combine the scalability of mouse gastruloids with a single-cell CRISPR screening platform to functionally dissect germ layer specification at single-cell transcriptomic resolution. Focusing on post-transcriptional regulation, we systematically map drivers of mesodermal and endodermal fate and identify the deadenylase Cnot8. Loss of Cnot8 leads to widespread poly(A) tail elongation and transcript stabilization, shifting mesoderm differentiation toward ectopic notochord fate, thereby profoundly impacting axial patterning. Collectively, our findings identify mRNA deadenylation as a fundamental mechanism linking cellular identity with morphogenetic signaling during mammalian body plan formation.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids 97%
- Primordial germ cell DNA demethylation and development require DNA translesion synthesis. 96%
- Single cell transcriptomics reveals a signaling roadmap coordinating endoderm and mesoderm lineage diversification during foregut organogenesis 96%
Similar papers in this journal
- Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons 96%
- Lineage hierarchies and stochasticity ensure the long-term maintenance of adult neural stem cells 96%
- Methylome inheritance and enhancer dememorization reset an epigenetic gate safeguarding embryonic programs 96%
Similar papers in this journal
- The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate 96%
- Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer. 95%
- Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.