Tissue identity is the dominant determinant of cross-species transferability of a porcine developmental programme.

Journal: BMC genomics
Published Date:

Abstract

BACKGROUND: Reproducibility and cross-species translation using the domestic pig (Sus scrofa) are limited by the lack of a standardised molecular framework for biological maturation: the pig's developmental tempo differs substantially from the human's, yet no tissue-resolved transcriptomic staging system exists. Synchronising porcine and human maturation is essential to move preclinical research from descriptive to predictive. RESULTS: We built a transcriptomic atlas of porcine development across five tissues (muscle, brain, liver, blood, lung) from 1,924 PigGTEx RNA-seq profiles. A single partial-least-squares (PLS) regressor staged each tissue at its native ordinal resolution and also drove cross-species transfer and biomarker extraction. Our central result: transfer of a pig-trained developmental score to other species is dominated by tissue identity, with phylogenetic distance a weaker secondary effect. Projected onto the seven-species Cardoso-Moreira atlas, transfer was strongest for brain and heart ([Formula: see text]-0.92) and weakest for the labile liver and ovary ([Formula: see text] and 0.42). Brain and heart stayed high even from pig to chicken ([Formula: see text] across ∼320 Myr), whereas liver and ovary collapsed. A variance partition confirmed the ranking (organ Type-II [Formula: see text], [Formula: see text]; phylogeny significant only at the species level, Spearman [Formula: see text], [Formula: see text], [Formula: see text]). The score independently confirmed lung, muscle, and adipose on the human dGTEx resource ([Formula: see text]-0.67) against an ortholog-scramble null and three controls. Because it is fit on pig and projected onto foreign-batch atlases, the transfer cannot arise from a pig-side artefact. A web application is available at https://pigdevstage.streamlit.app. CONCLUSIONS: The porcine developmental programme transfers to humans and more distant amniotes in a tissue-dependent manner, so the pig's value as a developmental model is set by how conserved each organ's developmental logic is, not by phylogenetic proximity. Validated on foreign-species atlases, the transfer sidesteps the stage-study confound that bounds within-pig staging to muscle and liver. The atlas is therefore best used organ by organ: strong for conserved organs (brain, heart) and weak for labile ones (liver).

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