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November 20, 2025iMeta4 citationsOpen Access

Single‐nucleus RNA sequencing reveals RUNX1 regulation of muscle hypertrophy through PI3K/AKT/mTOR pathway

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CWChenxu WangJMJunjie MaYWY. N. Wang

Key Result

RUNX1 promotes myotube hypertrophy by transcriptionally repressing Pik3r1, destabilizing PTEN, and activating the PI3K/AKT/mTOR signaling cascade.

Structured PICO

P
Population
Broiler chickens from neonatal to adult stages evaluated for pectoral muscle development using single-nucleus RNA sequencing.
I
Intervention
Loss-of-function assays targeting RUNX1
O
Outcome
Muscle hypertrophy and activation of the PI3K/AKT/mTOR signaling cascadesurrogate

RUNX1 plays a critical regulatory role in skeletal muscle hypertrophy through the PI3K/AKT/mTOR pathway, offering insights into muscle development.

Abstract

We used snRNA-seq to construct a high-resolution atlas of pectoral muscle development in broiler chickens from neonatal to adult stages. This analysis revealed pronounced molecular heterogeneity among satellite cells across developmental phases and uncovered a previously uncharacterized Runx1+ satellite cell subpopulation. By integrating pseudotime trajectory reconstruction, gene set enrichment analysis, dynamic expression profiling and loss-of-function assays, we established a critical regulatory role for RUNX1 in muscle hypertrophy. Mechanistically, RUNX1 promotes myotube hypertrophy by transcriptionally repressing Pik3r1, thereby reducing PI3K p85α levels, destabilizing PTEN, and activating the PI3K/AKT/mTOR signaling cascade, which enhances protein synthesis and drives myotube growth.

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Cite This Study

Wang et al. (2025) studied Muscle hypertrophy. RUNX1 was evaluated on Myotube hypertrophy and protein synthesis. RUNX1 promotes myotube hypertrophy by transcriptionally repressing Pik3r1, destabilizing PTEN, and activating the PI3K/AKT/mTOR signaling cascade.

synapsesocial.com/papers/6aa505636ab07c8cae811e33https://doi.org/10.1002/imt2.70093
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