WNT-mediating TCF/LEF transcription factor gene expression in early human pluripotency and cell lineages differs from the rodent paradigm

Abstract

Embryonic stem cell research has uncovered different requirements for WNT/{beta}-catenin signalling in human naive pluripotent cells compared to the mouse paradigm. It is therefore important to study WNT/{beta}-catenin signalling directly in models of early human development. Since TCF/LEF factors mediate the regulation of target genes downstream of WNT/{beta}-catenin signalling, we studied the expression and protein localisation of the four TCF/LEF genes by analysing in vitro "snapshots" of human development, leveraging naive and primed pluripotent cells as well as extraembryonic and early embryonic cell lineages. Strikingly, we comprehensively confirm clear differences between mouse and human pluripotent stem cells, suggesting species-specific requirements for WNT signalling that may reflect differences in states of pluripotency. Human naive ES cells express very low TCF7L1, unlike their mouse counterparts. TCF7L2 is robustly expressed in human naive ES-derived trophectoderm cells. In human primed pluripotent stem cells, activation of WNT/{beta}-Catenin signalling is required to induce expression of both TCF7 and LEF1, concomitant with hallmark gastrulation markers. This expression of human TCF/LEF genes benchmarks differential requirements for WNT/{beta}-catenin signalling throughout early human embryo development that requires further investigation.