Figure 3. Genetic variation of muscle cell proportions and coregulated cross-tissue processes.

(A) Uniform Manifold Approximation and Projection (UMAP) for skeletal muscle single-cell sequencing used to deconvolute proportions. (B) Mean relative proportions of pseudo-single-cell muscle cell compositions (denoted by color) between sexes. (C) Number of significant cross-tissue correlations (y-axis) corresponding to each skeletal muscle type in each sex (x-axis). Target tissues are distinguished by color, where NS (male platelets) denotes that no significant cross-tissue correlations were observed. (D) Heatmap showing significance of correlations between skeletal muscle hormone receptors and cell proportions, * = p < 0.01. (E) The strongest enriched myokines are plotted for each myokine (y-axis, −log10 p-value of myokine ~ cell composition) are shown for each muscle proportion for each sex (x-axis). Gene symbols for myokines are shown above each line, where red lines indicate positive correlations between myokine and cell type and blue shows inverse relationships. (F) Significant cross-tissue correlated genes in liver (blue) and pancreas (purple) for muscle fast-twitch glycolytic fibers (p < 1e-6) were used for overrepresentation tests where enrichment ratio of significance (x-axis) is shown for each pathway and sex (y-axis). (G) Heatmap showing the regression significance of the top five genes corresponding to inflammation (liver), exocytosis (liver), and protein synthesis (pancreas) for proportions of fast-twitch fiber type (un-adj). Below each correlation between fast-twitch fiber and liver or pancreas gene, the same regressions were performed while adjusting for abundance of select myokines in each sex. * = p < 1e-6.

Figure 3—figure supplement 1. Comparisons of deconvolution methods.

Cell proportions were estimated from skeletal muscle sequencing across the 310 individuals in GTEx.

Here, comparisons of the three most common methods (DCQ, NNLS, and porportionsInAdmixture) were plotted for each pseudo-sc-proportion, where proportionsInAdmixture method captured the largest relative number of cell types.

Figure 3—figure supplement 2. Cell composition correlations within each sex.

Heatmaps showing regressions for cell proportions in males (left) or females (right), * = regression p-value < 0.01.