Related Experiment Video
Updated: Jan 19, 2026
Cell Fate Reprogramming of Nematode Germ Cells into Neurons
Tox4 modulates cell fate reprogramming
Lotte Vanheer1, Juan Song1, Natalie De Geest1
1KU Leuven - University of Leuven, Department of Development and Regeneration, Herestraat 49, B-3000 Leuven, Belgium.
Abstract:
Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified Tox4 as a novel factor that modulates cell fate through an assay that determined the efficiency of iPSC reprogramming. We found that Tox4 is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of the reprogramming conditions used. Tox4 enables proper exogenous reprogramming factor expression, and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that the TOX4 protein assembles into a high molecular form. Moreover, Tox4 is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of Tox4 in modulating cell fate. Our study reveals Tox4 as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.This article has an associated First Person interview with the first author of the paper.
Insights
Tox4 is a novel gene crucial for cell fate reprogramming. It facilitates the efficient conversion of somatic cells into induced pluripotent stem cells (iPSCs) and neuronal cells.
Area of Science:
- Cell Biology
- Developmental Biology
- Stem Cell Research
Background:
- Cellular reprogramming allows somatic cells to become induced pluripotent stem cells (iPSCs).
- The precise molecular mechanisms and key mediators governing this reprogramming process are not fully understood.
Purpose of the Study:
- To identify novel genes and understand the mechanisms involved in somatic cell reprogramming into iPSCs.
- To investigate the role of candidate genes in modulating cell fate transitions.
Main Methods:
- Utilized siRNA-mediated knockdown of candidate genes during somatic cell reprogramming.
- Employed assays to measure the efficiency of induced pluripotent stem cell reprogramming.
- Analyzed the expression of reprogramming factors and the dynamics of enhancer activity.
Main Results:
- Identified Tox4 as a novel factor essential for efficient iPSC reprogramming.
- Demonstrated that Tox4 is required early in reprogramming to generate intermediates, regardless of conditions.
- Showed Tox4's role in regulating reprogramming factor expression and enhancer accessibility.
- Confirmed Tox4's necessity for fibroblast-to-neuron conversion, indicating a broader cell fate modulation role.
Conclusions:
- Tox4 is a novel transcriptional modulator that mediates cell fate reprogramming.
- Tox4 plays a critical role in the transition from somatic to pluripotent and neuronal cell states.
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