# Splice choices at the threshold of activation: Alternative splicing fine-tunes Notch signaling in muscle stem cells

**Authors:** Holly Jiogo, Colin Crist

PMC · DOI: 10.1016/j.stemcr.2025.102782 · Stem Cell Reports · 2026-01-13

## TL;DR

The paper shows how alternative splicing regulates Notch signaling in muscle stem cells through a specific RNA-binding protein and exon inclusion.

## Contribution

The study reveals a novel RBFOX2-dependent splicing event in Numb that fine-tunes Notch signaling during muscle stem cell activation.

## Key findings

- Alternative splicing is widespread during muscle stem cell activation.
- RBFOX2-dependent splicing of Numb regulates Notch signaling.
- Exon inclusion in Numb tunes the transition from quiescence to activation.

## Abstract

Alternative splicing events have emerged as a rapid regulatory layer in gene expression. Lin et al. demonstrate that alternative splicing is widespread during muscle stem cell activation. Its functional importance is illustrated through an RNA-binding fox 1-homolog 2 (RBFOX2)-dependent splice choice in the Notch regulator Numb, showing how inclusion of a single exon can tune Notch signaling to regulate the transition from quiescence to activation.

Alternative splicing events have emerged as a rapid regulatory layer in gene expression. Lin et al. demonstrate that alternative splicing is widespread during muscle stem cell activation. Its functional importance is illustrated through an RNA-binding fox 1-homolog 2 (RBFOX2)-dependent splice choice in the Notch regulator Numb, showing how inclusion of a single exon can tune Notch signaling to regulate the transition from quiescence to activation.

## Linked entities

- **Genes:** RBFOX2 (RNA binding fox-1 homolog 2) [NCBI Gene 23543], NUMB (NUMB endocytic adaptor protein) [NCBI Gene 8650]

## Full-text entities

- **Genes:** NUMB (NUMB endocytic adaptor protein) [NCBI Gene 8650] {aka C14orf41, S171, c14_5527}, RBFOX1 (RNA binding fox-1 homolog 1) [NCBI Gene 54715] {aka 2BP1, A2BP1, FOX-1, FOX1, HRNBP1}, RBFOX2 (RNA binding fox-1 homolog 2) [NCBI Gene 23543] {aka FOX2, Fox-2, HNRBP2, HRNBP2, RBM9, RTA}

## Full text

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## Figures

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## References

11 references — full list in the complete paper: https://tomesphere.com/paper/PMC12925942/full.md

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Source: https://tomesphere.com/paper/PMC12925942