A new collaborative work by the Computational Genomics Group (Nikolaou lab) on the role of Wnt/Tc7l1 in cell differentiation.
A collaborative study between the lab of Frederic Lluis at KU Leuven and BSRC “Alexander Fleming” Computational Genomics Group (Nikolaou lab) was recently published in Nature Communications.
The work attempts to elucidate the role of the transcriptional repressor Tcf7l1 in driving Primitive Endoderm (PE) formation by antagonizing naïve and formative pluripotency. The role of the Wnt/Tcf7l1 axis in this process is shown to be rather intricate. Through a series of single-cell and bulk RNASeq analyses, coupled with embryo pre-implantation assays, the authors showed that PE cell fate specification is preceded by naive and formative pluripotency repression by Tcf7l1. Additional ChIPSeq analyses showed that this is indeed taking place through the binding of Tcf7l1 to pluripotency gene promoters and their subsequent repression. Its role, thus, appears to be a sensible, permissive, "gatekeeper" that suppresses pluripotency and drives PE formation.
Taken together this work highlights the importance of transcriptional Wnt inhibition in regulating lineage specification in ESCs and identifies Tc7l1 as a key regulator of this process.
Athanasouli, P., Balli, M., De Jaime-Soguero, A. et al. The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency. Nature Communications 14, 1210 (2023). https://doi.org/10.1038/s41467-023-36914-1