Transcriptome and Metabolome Integration Provides New Insights Into the Regulatory Networks of Tibetan Pig Alveolar Type II Epithelial Cells in Response to Hypoxia

Abstract

Tibetan pigs show a widespread distribution in plateau environments and exhibit striking physiological and phenotypic differences from others pigs for adaptation to hypoxic conditions. However, the regulation of mRNAs and metabolites as well as their functions in the alveolar type II epithelial (ATII) cells of Tibetan pigs remain undefined. Herein, we carried out integrated metabolomic and transcriptomic profiling of ATII cells between Tibetan pigs and Landrace pigs across environments with different oxygen levels to delineate their signature pathways. We observed that the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) profiles displayed marked synergy of hypoxia-related signature pathways in either Tibetan pigs or Landrace pigs. A total of 1,470 DEGs shared between normoxic (TN, ATII cells of Tibetan pigs were cultured under 21% O2; LN, ATII cells of Landrace pigs were cultured under 21% O2) and hypoxic (TL, ATII cells of Tibetan pigs were cultured under 2% O2; LL, ATII cells of Landrace pigs were cultured under 2% O2) groups and 240 DAMs were identified. Functional enrichment assessment indicated that the hypoxia-related genes and metabolites were primarily involved in glycolysis and aldosterone synthesis and secretion. We subsequently constructed an interaction network of mRNAs and metabolites related to hypoxia, such as guanosine-3′, 5′-cyclic monophosphate, Gly-Tyr, and phenylacetylglycine. These results indicated that mitogen-activated protein kinase (MAPK) signaling, aldosterone synthesis and secretion, and differences in the regulation of MCM and adenosine may play vital roles in the better adaptation of Tibetan pigs to hypoxic environments relative to Landrace pigs. This work provides a new perspective and enhances our understanding of mRNAs and metabolites that are activated in response to hypoxia in the ATII cells of Tibetan pigs.

Conjoint analysis of transcriptome and metabolome profiles of normal captivity and arch soil free-range in Meishan pigs

“…Accordingly, in this study Meishan piglets were used as an experimental model to compare how differences in rearing conditions (NC vs. ASF) would impact immune status. Many other metabolomic and transcriptomic studies of pigs exposed to environmental stressors have been published to date ( 11 , 30 ). This study, however, is the first to our knowledge to conduct an integrated metabolomic and transcriptomic analysis in Meishan pigs, highlighting phenotypes that are dependent on rearing conditions.…”

“…Raw data were processed as in a prior report ( 11 ). Briefly, Proteowizard (v 3.0.8789) converted these raw data files into the mzXML format, after which peak identification, filtration, and alignment were conducted with the R (v3.3.2) XCMS package ( 12 ) using the following settings: bw = 5, ppm = 15, peakwidth = c (5,30), mzwid = 0.01, mzdiff = 0.01, method = “centWave.” Subsequent analyses were then performed based on the m/z ratio, retention time, intensity, and positive/negative precursor ions.…”

Ssc-miR-141 Attenuates Hypoxia-Induced Alveolar Type II Epithelial Cell Injury in Tibetan Pigs by Targeting PDCD4

“…A newborn Tibetan piglet was selected and slaughtered under aseptic conditions after anesthesia to collect the lung tissue. Primary ATII cells were isolated from the lungs according to the method of Yang et al [ 35 ]. Isolated ATII cells were randomly divided into two groups, namely the control group (21% O 2 , normoxia) and experimental group (2% O 2 , hypoxia).…”

Integrated analysis of transcriptome and metabolome revealed biological basis of sows from estrus to lactation

“… 14 Analysis of the combined transcriptome and metabolome provides the information to interpret key molecules from genes to phenotypes. In pigs, some combined transcriptome and metabolome studies for important economic traits or drug reactions have been reported, such as feed efficiency, 15 hypoxia-related signature, 16 and the responses of pigs orally inoculated with amoxicillin solution, 17 while studies on metabolites in various stages of pregnancy are still quite a few. Therefore, characterizing the molecular mechanisms of the reproduction and lactation process of pigs based on the transcriptome and metabolome data will be very necessary and can be a useful model for human pregnancy disorders.…”