Single-Nucleus RNA Sequencing Identifies CREM as a Brake on Myofiber Hypertrophy in Chickens.
4 affiliations
- 1National Engineering Laboratory for Animal Breeding, Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
- 2Department of Animal Genetics and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, China.
- 3State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
- 4LC-Bio Technology Co. Ltd., Hangzhou, China.
Abstract
Myofiber hypertrophy is central to economically important agricultural traits and vertebrate development, yet the underlying cellular and molecular programs remain elusive. Chickens have undergone substantial divergence in muscle growth following decades of artificial selection, making them a unique model for dissecting these mechanisms at single-cell resolution. Here, we performed singlenucleus RNA sequencing on 91 144 nuclei from postnatal chicken pectoralis major. Eight major conserved cell populations were resolved, with temporal dynamics exhibiting divergence between fast-growing broilers and slow-growing layers. A novel terminally differentiated myocyte subpopulation (AK1⁺ myocytes) was markedly enriched in slow-growing birds. Analysis revealed that accelerated myoblast expansion and delayed terminal differentiation are primary drivers of myofiber hypertrophy, supported by a pro-growth niche involving IGF-signaling FAPs and macrophage-myogenic crosstalk. Further comprehensive analyses identified CREM as a master repressor of myofiber hypertrophy. Mechanistically, CREM directly binds and transcriptionally activates the JUN promoter, and both factors cooperatively sustain the expression of growth inhibitors MSTN, FBXO32, and TRIM63. In vivo and in vitro functional validation confirmed that CREM deletion promotes myofiber hypertrophy, increasing pectoralis major weight and percent by 29.96% and 20.50%, respectively. This study uncovers CREM as a novel brake on myofiber hypertrophy, offering fundamental insights into vertebrate skeletal muscle development.
Related
- Myofiber-specific knockout of TGF-β type I receptors in mice concurrently drives muscle hypertrophy, oxidative metabolism, and absolute force
- IndelQuant: A Workflow for Cost-Efficient Amplicon Sequencing Analysis of Genome-Edited Chickens
- Complementary single-nucleus and single-cell RNA sequencing reveal tumor state evolution and microenvironmental rewiring in NSCLC
- Single-nucleus RNA sequencing in ischemic cardiomyopathy reveals common transcriptional profile underlying end-stage heart failure
- Protocol for minimized-bias profiling of liver and visceral adipose tissue in mice using integrated single-nucleus RNA sequencing
BibTeX
@article{gu2026singlenucleus,
title = {{Single-Nucleus RNA Sequencing Identifies CREM as a Brake on Myofiber Hypertrophy in Chickens.}},
author = {Shuang Gu and Xiyu Zhao and Zheyi Jiang and Chaoliang Wen and Chaoyi Wang and Qiulian Wang and Qiang Huang and Fangren Lan and Shenghui Wu and Junying Li and Congjiao Sun and Huadong Yin and Ning Yang},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78534},
url = {https://europepmc.org/article/MED/42949767},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-Nucleus RNA Sequencing Identifies CREM as a Brake on Myofiber Hypertrophy in Chickens.
AU - Shuang Gu
AU - Xiyu Zhao
AU - Zheyi Jiang
AU - Chaoliang Wen
AU - Chaoyi Wang
AU - Qiulian Wang
AU - Qiang Huang
AU - Fangren Lan
AU - Shenghui Wu
AU - Junying Li
AU - Congjiao Sun
AU - Huadong Yin
AU - Ning Yang
PY - 2026
DA - 2026/10/28
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78534
UR - https://europepmc.org/article/MED/42949767
AB - Myofiber hypertrophy is central to economically important agricultural traits and vertebrate development, yet the underlying cellular and molecular programs remain elusive. Chickens have undergone substantial divergence in muscle growth following decades of artificial selection, making them a unique model for dissecting these mechanisms at single-cell resolution. Here, we performed singlenucleus RNA sequencing on 91 144 nuclei from postnatal chicken pectoralis major. Eight major conserved cell populations were resolved, with temporal dynamics exhibiting divergence between fast-growing broilers and slow-growing layers. A novel terminally differentiated myocyte subpopulation (AK1⁺ myocytes) was markedly enriched in slow-growing birds. Analysis revealed that accelerated myoblast expansion and delayed terminal differentiation are primary drivers of myofiber hypertrophy, supported by a pro-growth niche involving IGF-signaling FAPs and macrophage-myogenic crosstalk. Further comprehensive analyses identified CREM as a master repressor of myofiber hypertrophy. Mechanistically, CREM directly binds and transcriptionally activates the JUN promoter, and both factors cooperatively sustain the expression of growth inhibitors MSTN, FBXO32, and TRIM63. In vivo and in vitro functional validation confirmed that CREM deletion promotes myofiber hypertrophy, increasing pectoralis major weight and percent by 29.96% and 20.50%, respectively. This study uncovers CREM as a novel brake on myofiber hypertrophy, offering fundamental insights into vertebrate skeletal muscle development.
SN - 2198-3844
ER -