PSIV-23 Transcriptomic analysis revealed the mechanisms of resilience and susceptibility to nonalcoholic steatohepatitis in dairy goats under high-concentrate diet
Bibliographic record
Abstract
Abstract Liver health is vital for growth and health of ruminants, which can directly affect their performance. High-concentrate diet (HCD) feeding, a common practice to meet the energy requirements for animal production and growth, has been known to induce liver damage, including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in ruminants. To date, the regulatory mechanisms of liver metabolic dysfunctions in ruminants induced by HCD are not well defined. To elucidate molecular regulatory mechanisms underlying liver dysfunction in ruminants, we compared liver transcriptome and single-cell transcriptome of dairy goats that had varied responses to the HCD, aiming to underpin the key mechanisms behind resilience and susceptibility to NASH in ruminants. After feeding 30 dairy goats with low-concentrate diet (LCD, n = 15, defined as Con) or high-concentrate diet (HCD, n = 15) for 6 wk, 10 of them developed NASH (defined as NASH), while the other 5 did not showed any NASH symptom (defined as NASH-tolerance, NASH-T) under HCD. Liver tissues were collected to extract RNA. The paired-end RNA-seq library was sequenced with a NovaSeq6000 sequencer (Illumina). Real-time quantitative PCR was conducted to verify the significantly different genes among groups. Liver single-cell transcriptome was performed using 10×Genomics Chromium system. Liver transcriptome analysis revealed that the expression level of genes involved in the interleukin (IL)-17 signaling pathway, including IL-17A (P = 0.035; 0.001), Act1 (P = 0.036; 0.002), FOSB (P = 0.041; 0.048) and IL-1β (P = 0.022; 0.002) in the NASH group were significantly greater than those in the Con and NASH-T groups. Hepatic single-cell RNA sequencing identified seven cell types in the liver, including hepatocytes, macrophages, T cells, endothelial cell, natural killer (NK) cell, hepatic stellate cells (HSCs), B cells. In T cell subset, significantly decreased T helper 17 (TH17) cells and increased regulatory T (Treg) cells were detected in the NASH group compared with Con and NASH-T groups. In TH17 cell, the expression levels of IL-17A (P = 0.004; 0.009) and IL-23R (P = 0.007; 0.01; the surface antibodies of TH17 cells) in NASH group were significantly greater than those in the Con and NASH-T groups. The expression levels of Foxp3 (P < 0.001; 0.013), IL-2R (P < 0.001; 0.001), CTLA-4 (P = 0.005; 0.017) and CD127 (P = 0.004; 0.009; the surface antibodies of Treg cells) in NASH group were significantly less than those in the Con and NASH-T groups. Our results revealed the role of liver immune cells in maintaining tolerance to NASH in dairy goats under HCD, which provides new understanding in pathogenesis of NASH under HCD. Further studies are needed to identify major factors that drive the changes of ratio of TH17/Treg cell.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".