Global Long Noncoding RNA and mRNA Expression Changes between Prenatal and Neonatal Lung Tissue in Pigs

Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310 lncRNAs and 14,579 mRNAs were identified and substantially expressed. Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value ≤ 0.05, FDR: False Discovery Rate) differentially expressed and were mainly enriched in categories related to cell proliferation, immune response, hypoxia response, and mitochondrial activation. For example, CCNA2, an important gene involved in the cell cycle and DNA replication, was upregulated in neonatal lungs. We also identified 452 significantly (FDR-adjusted p value ≤ 0.05) differentially expressed lncRNAs, which might function in cell proliferation, mitochondrial activation, and immune response, similar to the differentially expressed mRNAs. These results suggest that differentially expressed mRNAs and lncRNAs might co-regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA might promote distal lung development by up-regulating the heparin-binding epidermal growth factor-like (HB-EGF) expression. Our research provides basic lung development datasets and will accelerate clinical researches of newborn lung diseases with pig models. Six female Tibetan-Meishan (Patriarchal: Tibetan pig; Matriarchal: Meishan pig) hybrid piglets were used to simulate the adaptation of newborns. The pregnancy period was considered to be 113 days. The fetal group consisted of three piglets obtained from three pregnant sows of similar weights on the last day before birth. The neonatal group consisted of three piglets of similar weight obtained two days after birth from another three pregnant sows. All parents were of a similar-weight and were raised under the same feeding and rearing conditions until caesarean and parturition. Piglet lung tissues were rapidly sampled from each carcass and selectively separated into two parts. One part was fixed with 10% formalin for morphometric analysis, and the other part frozen immediately in liquid nitrogen and stored at −80 °C until required for RNA extraction, sequencing and transcriptome analysis.