Usage Information
Abstract
Pathological cardiac remodeling is associated with the reactivation of fetal genes, yet the extent of the heart’s fetal gene program and its impact on proteome compositions remain incompletely understood. Here, using a proteome-wide protein ratio quantification strategy with mass spectrometry, we identified pervasive isoform usage shifts in fetal and postnatal mouse hearts, involving 145 pairs of highly homologous paralogs and alternative splicing–derived isoform proteins. Proteome-wide ratio comparisons readily rediscovered hallmark fetal gene signatures in muscle contraction and glucose metabolism pathways, while revealing what we believe to be previously undescribed isoform usage in mitochondrial and gene-expression-regulating proteins, including PPA1/PPA2, ANT1/ANT2, and PCBP1/PCBP2 switches. Paralogs with differential fetal usage tend to be evolutionarily recent, consistent with functional diversification. Alternative splicing adds another rich source of fetal isoform usage differences, involving PKM M1/M2, GLS1 KGA/GAC, PDLIM5 long/short, and other spliceoforms. When comparing absolute protein proportions, we observed a partial reversion toward fetal gene usage in pathological hearts. In summary, we present a ratiometric catalog of paralogs and spliceoform pairs in the cardiac fetal gene program. More generally, the results demonstrate the potential of applying the proteome-wide ratio test concept to discover new regulatory modalities beyond differential gene expression.
Authors
Yu Han, Shaonil Binti, Sara A. Wennersten, Boomathi Pandi, Dominic C.M. Ng, Edward Lau, Maggie P.Y. Lam
Usage data is cumulative from August 2025 through April 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 2,065 | 77 |
| 458 | 15 | |
| Figure | 598 | 0 |
| Supplemental data | 673 | 12 |
| Citation downloads | 160 | 0 |
| Totals | 3,954 | 104 |
| Total Views | 4,058 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
