Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Embryonic Development

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1645959

Differential regulation of gene co-expression modules in muscles and liver of preterm newborns

Provisionally accepted
Jan  KopeckyJan Kopecky1*Petra  JanovskaPetra Janovska1Tatyana  KobetsTatyana Kobets1Lenka  Steiner MrazovaLenka Steiner Mrazova2Michaela  SvobodovaMichaela Svobodova1Markéta  TesarováMarkéta Tesarová3Pavel  KopeckyPavel Kopecky3Petr  ZouharPetr Zouhar1Martin  RossmeislMartin Rossmeisl1Viktor  StraneckyViktor Stranecky2Stanislav  KmochStanislav Kmoch2
  • 1Fyziologicky ustav Akademie ved Ceske republiky, Prague, Czechia
  • 2Univerzita Karlova laborator pro studium vzacnych onemocneni, Prague, Czechia
  • 3Univerzita Karlova 1 lekarska fakulta, Prague, Czechia

The final, formatted version of the article will be published soon.

Background Newborns undergo rapid metabolic and organ adaptations after birth, which are compromised in premature newborns, leading to adverse health outcomes. Molecular mechanisms underlying these transitions remain poorly understood due to limited tissue availability. To address this gap, we characterized tissue transcriptomes using autopsy samples from a unique newborn cohort. Methods We analyzed liver (LI), heart (HM), and skeletal muscle (SM) transcriptomes using RNA sequencing in 41 predominantly premature newborns who died shortly after birth. Nearly 14,000 protein-coding gene transcripts per tissue were detected. Results Tissues exhibited distinct expression profiles, with LI showed the highest number of tissue-specific genes. SM gene expression correlated strongly with gestational age at birth (i.e., the prenatal development), while LI was influenced by the duration of postnatal survival (i.e., the postnatal development). HM displayed minimal changes, suggesting stable myocardial metabolism during the perinatal transition. Weighted Gene Co-expression Network Analysis (WGCNA) identified tissue-specific gene co-expression modules were linked to clinical traits such as gestational age, birth weight, survival duration, nutrition, and exposure to catecholamine treatment. The key functional annotations, validated by differential expression analysis, revealed that LI and SM modules were enriched for mitochondrial metabolism and oxidative phosphorylation genes, with more pronounced prenatal development in SM, and a postnatal increase in both tissues. Data suggests that energy metabolism in SM matures first, followed by the development of muscle functions. Hepatic modules were associated with a postnatal increase in the steroid hormone/xenobiotic metabolism, and a decline in hematopoietic activity. Robust annotations to ribosome activity suggested tissue-specific changes in protein synthesis, which declined prenatally in SM, postnatally in HM. Notably, the supply of exogenous glucose and nutrition type were strongly associated with hepatic gene expression, highlighting the central role of the liver in postnatal metabolic adaptation. Conclusions Overall, our study highlights tissue-specific perinatal gene regulation, with mitochondrial maturation emerging as a crucial driver of postnatal adaptation, explaining vulnerabilities in preterm infants. We provide a unique resource for characterizing developmental changes in tissue transcriptomes during the fetal-to-neonatal transition in human newborns.

Keywords: tissue transcriptome, human, Premature newborn, WGCNA, Mitochondria

Received: 14 Jun 2025; Accepted: 02 Sep 2025.

Copyright: © 2025 Kopecky, Janovska, Kobets, Steiner Mrazova, Svobodova, Tesarová, Kopecky, Zouhar, Rossmeisl, Stranecky and Kmoch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jan Kopecky, Fyziologicky ustav Akademie ved Ceske republiky, Prague, Czechia

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.