William Peidong Gao

William Peidong Gao

Ph.D. candidate in Genetics at Case Western Reserve University. I work on bioinformatics, multi-omics, human islet biology, and diabetes.

A single-cell atlas of bovine skeletal muscle reveals mechanisms regulating intramuscular adipogenesis and fibrogenesis

Published in Journal of Cachexia, Sarcopenia and Muscle, 2023

Co-first author

Leshan Wang, Peidong Gao, Chaoyang Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth McMillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

* These authors contributed equally.

Read the paper · DOI: 10.1002/jcsm.13292

The Question

Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are major determinants of beef quality, and both accumulate in human myopathies and during aging. Their regulation in large mammals remained poorly understood.

Can beef cattle serve as a model for IMF and IMC accumulation, and which cells determine the balance between the two?

What the study showed

Single-cell RNA sequencing of 32,708 cells from Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman crossbred calves resolved 21 cell types.

Bovine FAPs are a heterogeneous population. Sub-clustering identified an adipogenic subpopulation enriched for COL4A1 and CFD in the endomysium, and a fibrogenic subpopulation enriched for COL1A1 and POSTN in the perimysium, both arising from a shared unspecified progenitor. Wagyu FAPs showed more advanced adipogenic programming and Brahman FAPs more advanced fibrogenic programming, consistent with each breed.

Integrated analysis with published human and non-human primate datasets identified CFD as a regulator common to both species. It predicted adult IMF from young cattle (R² = 0.885) and was elevated in aged humans with metabolic syndrome and in patients with Duchenne muscular dystrophy.

My role

I performed all of the single-cell analysis, from raw data to the reported results: atlas construction and cell-type annotation, the FAP sub-population and trajectory analysis, and the cross-species integration.