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Tibetan cashmere goats are not only served as a valuable model for studying adaptation to hypoxia and high-altitude conditions but also playing a pivotal role in bolstering local economies through the provision of premium quality cashmere yarn. In this study, we performed an integration and network analysis of metabolomic, transcriptomic and proteomic to elucidate the role of differentially expressed genes, important metabolites, and relevant cellular and metabolic pathways between the fine (average 12.04 ± 0.03 μm of mean fiber diameter) and coarse cashmere (average 14.88 ± 0.05 μm of mean fber diameter) producing by Tibetan cashmere goats. We identified a distinction of 56 and 71 differential metabolites (DMs) between the F and C cashmere groups under positive and negative ion modes, respectively. The KEGG pathway enrichment analysis of these DMs highlighted numerous pathways predominantly involved in amino acid and protein metabolism, as indicated by the finding that the most impactful pathway was the mammalian target of rapamycin (mTOR) signalling pathway. In the F group, we identified a distinctive metabolic profile where amino acid metabolites including serine, histidine, asparagine, glutamic acid, arginine, valine, aspartic acid, tyrosine, and methionine were upregulated, while lysine, isoleucine, glutamine, tryptophan, and threonine were downregulated. The regulatory network and gene co-expression network revealed crucial genes, metabolites, and metabolic pathways. The integrative omics analysis revealed a high enrichment of several pathways, notably encompassing protein digestion and absorption, sphingolipid signalling, and the synaptic vesicle cycle. Within the sphere of our integrative analysis, DNMT3B was identified as a paramount gene, intricately associated with significant proteins such as HMCN1, CPB2, GNG12, and LRP1. Our present study delineated the molecular underpinnings governing the variations in cashmere characteristics by conducting comprehensive analyses across metabolomic, transcriptomic, and proteomic dimensions. This research provided newly insights into the mechanisms regulating cashmere traits and facilitated the advancement of selective breeding programs aimed at cultivating high-quality superfine Tibetan cashmere goats., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tibetan cashmere goats are served as a valuable model for high altitude adaptation and hypoxia complications related studies, while the cashmere produced by these goats is an important source of income for the herders. The aim of this study was to investigate the differences in protein abundance underlying the fine (average 12.20 ± 0.03 μm of mean fiber diameter) and coarse cashmere (average 14.67 ± 0.05 μm of mean fiber diameter) producing by Tibetan cashmere goats. We systematically investigated the genetic determinants of fiber diameter by integrated analysis with proteomic and transcriptomic datasets from skin tissues of Tibetan cashmere goats., Results: We identified 1980 proteins using a label-free proteomics approach. They were annotated to three different databases, while 1730 proteins were mapped to the original protein coding genes (PCGs) of the transcriptomic study. Comparative analyses of cashmere with extremely fine vs. coarse phenotypes yielded 29 differentially expressed proteins (DEPs), for instance, APOH, GANAB, AEBP1, CP, CPB2, GPR142, VTN, IMPA1, CTSZ, GLB1, and HMCN1. Functional enrichment analysis of these DEPs revealed their involvement in oxidation-reduction process, cell redox homeostasis, metabolic, PI3K-Akt, MAPK, and Wnt signaling pathways. Transcription factors enrichment analysis revealed the proteins mainly belong to NF-YB family, HMG family, CSD family. We further validated the protein abundance of four DEPs (GC, VTN, AEBP1, and GPR142) through western blot, and considered they were the most potential candidate genes for cashmere traits in Tibetan cashmere goats., Conclusions: These analyses indicated that the major biological variations underlying the difference of cashmere fiber diameter in Tibetan cashmere goats were attributed to the inherent adaptations related to metabolic, hypoxic, and stress response differences. This study provided novel insights into the breeding strategies for cashmere traits and enhance the understanding of the biological and genetic mechanisms of cashmere traits in Tibetan cashmere goats., (© 2022. The Author(s).)