# Max Perutz Labs: Wt1 splice isoforms bias lineage programmes in pluripotent cells before gastrulation

- Published: 2026-11-05 21:13 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: Wt1 splice isoforms, formative pluripotency, KTS splice status, CRISPRa screen, epiblast E5.5, gastrulation, OTX2 OCT4 FOXO1, human pluripotent cells, Max Perutz Labs
- URL: https://realtech.media/news/rt-85c5c07c7fc4593840281267_max_perutz_labs/

**Authors report that KTS splice status of Wt1 separates anterior/neuroectodermal from posterior/mesodermal programmes in cultured cells, with matching signs in the E5.5 epiblast.**

![Max Perutz Labs: Wt1 splice isoforms bias lineage programmes in pluripotent cells before gastrulation](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/4f47c032024fb4ea.jpg)
*Ryddragyn at English Wikipedia, Wikimedia Commons, Public domain*

A team from the Max Perutz Labs at the Vienna BioCenter (Austria) has described how the gene Wt1 influences lineage-associated transcriptional programmes during formative pluripotency, the stage before gastrulation. The paper, with Martin Leeb as corresponding author, was published on 4 November 2026 in Nature Communications. [1] Using a targeted CRISPRa screen, the authors identified Wt1 as a regulator of these programmes. [1]

The authors frame the work around an open question in mammalian development: how transcriptional asymmetry arises in the epiblast before gastrulation. [1]

## Wt1 in formative pluripotency

According to the study, Wt1 is transiently induced during formative pluripotency both in vitro and in vivo, coinciding with emerging lineage biases. [1] Precocious induction of Wt1 advanced cells toward post-implantation identity. [1]

Cells deficient in Wt1 still executed naïve exit, but they showed impaired acquisition of formative and lineage-associated programmes. [1] The authors also report that WT1 binds active regulatory elements together with OTX2, OCT4 and FOXO1. [1]

## Splice isoforms and anterior bias

The team compared Wt1 splice isoforms. KTS splice status emerged as the major determinant of divergent anterior/neuroectodermal and posterior/mesodermal transcriptional programmes in vitro. [1]

In the E5.5 epiblast, Wt1 expression and splice composition aligned with lineage-biased states. The authors link this isoform usage to anterior bias in vivo. [1] Isoform-dependent programmes were conserved in human pluripotent cells. [1]

From these results the authors conclude that alternative splicing is a mechanism tuning lineage-associated transcriptional bias before gastrulation. [1]

The data come from cell-culture experiments, an analysis of the E5.5 epiblast and human pluripotent cells. This is a fundamental study of early development, not a clinical one.

## Sources

1. [Nature Communications](https://doi.org/10.1038/s41467-026-79258-2)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-85c5c07c7fc4593840281267_max_perutz_labs/