The pituitary gland plays a pivotal role in regulating puberty and reproductive physiology; however, the precise cellular and molecular mechanisms driving the pubertal transition in large animal, such as ewes, remain poorly understood. Here, we generated a comprehensive single-cell transcriptomic atlas of the ovine anterior pituitary, specifically comparing the pre-pubertal (3 month) and post-pubertal (6 month) stages. We identified 30 335 cells classified into ten distinct clusters. Comparative analysis revealed a global transcriptional reprogramming during puberty, characterized by a marked upregulation of genes associated with ribosome biogenesis, unfolded protein response, and hormone secretion across endocrine cells, reflecting an expanded biosynthetic capacity. Specifically, we identified SCG2 as a critical regulator of gonadotroph maturation. Functional validation demonstrated that SCG2 facilitates the biogenesis of secretory granules, thereby promoting FSH synthesis and secretion. Furthermore, intercellular communication analysis uncovered a distinct shift in the pituitary microenvironment: the 6 month pituitary exhibited enhanced regulatory networks, including IGF signaling mediated by non-endocrine cells and NT signaling (e.g., BDNF-NTRK2) driven by multiple cell types. These findings suggest that the onset of puberty relies on a coordinated "endocrine-to-endocrine" and "non-endocrine-to-endocrine" crosstalk. This study provides a high-resolution molecular blueprint of the pubertal transition, highlighting the key roles of biosynthetic machinery upgrades and microenvironmental remodeling in establishing the high reproductive performance of Hu sheep.

Reproduction is a fundamental biological process regulated by complex cellular and molecular networks across the neuroendocrine and reproductive systems. To explore conserved and species-specific mechanisms of fertility regulation, we constructed a high-resolution single-cell transcriptomic atlas of 15 reproductive and central nervous system (CNS) tissues from sheep and integrated it with human single-cell datasets from 13 matched tissues. This comparative atlas comprises over 1.09 million cells and identifies 76 major cell types across species. Cross-species integration based on 15 748 orthologous genes revealed that 54 cell types (71.1%) are shared between sheep and humans, showing strong conservation in transcriptional programs, cell lineage trajectories, and regulatory networks. Integrating genome-wide association studies (GWAS) for sheep lifetime average litter size with the single-cell atlas identified crucial fertility-associated genes and signaling pathways. Cell-cell communication analysis revealed UNC5-SLIT-BMP signaling cascades coordinating neuroendocrine regulation of fertility along the hypothalamus-pituitary-ovary (HPO) axis. Trait-cell type enrichment analyses for 41 human complex traits further demonstrated that conserved reproductive and CNS cell types in sheep recapitulate key human GWAS associations. Together, this cross-species single-cell atlas (https://csca.njau.edu.cn/) provides a valuable resource for understanding how conserved cellular programs and inter-organ signaling networks regulate fertility and other complex traits.

In China, Hu sheep lambskin quality is largely determined by wool curvature, with wavy-wool lambs producing higher-quality pelts than straight-wool lambs. However, the genetic mechanisms underlying wool curvature formation remain poorly understood. To address this knowledge gap, we conducted whole-genome resequencing and transcriptomic analyses to identify candidate genes associated with wool curvature in Hu sheep. Phenotypic records from 3047 Hu lambs identified significant differences between wavy- and straight-wool groups. Twenty representative animals (10 per group) were selected for whole-genome resequencing. Selective sweep analyses based on the fixation index (FST), absolute log2-transformed nucleotide diversity ratio [|log2(π ratio)|], and Tajima's D (TajD) identified 157 genomic windows under positive selection. Four major genomic regions showing strong selective signatures were located on chromosomes 4, 7, 13, and 18. Several biologically relevant candidate genes were identified within these regions, including KRTDAP, FGF2, FGF7, OCLN, MAPK1, SHC4, LAMA2, and COL9A3. Functional enrichment analysis indicated that these genes are primarily associated with extracellular matrix (ECM) organization, focal adhesion, PI3K-Akt, MAPK, and Ras signaling pathways. In addition, RNA sequencing (RNA-seq) data from an independent cohort of eight lambs were integrated with genomic selection signals. This integrative analysis identified 61 overlapping genes, from which 12 high-confidence candidate genes were prioritized, including LUM, COL6A1, SPARC, ITGA11, and DCLK1. These findings highlight genomic regions and candidate genes potentially associated with ECM remodeling and other biological processes relevant to lambskin pattern formation, providing valuable genomic resources for future functional studies and marker-assisted selection in Hu sheep.

Sheep (Ovis aries) are valuable biomedical models for studying human reproductive biology, however, the transcriptional dynamics underlying their ovarian development remain insufficiently characterized. In this study, we profiled 61,649 single-cell transcriptomes from sheep ovarian tissues across key developmental stages: prenatal (E90), pre-puberty (M3), post-puberty (M6), and adulthood (Y2, Y4). We identified nine major cell types with distinct and dynamic gene expression patterns, highlighting significant developmental transitions. Notably, granulosa cells exhibited profound transcriptomic shifts, underscoring their critical role in oocyte maturation and follicular development. Key transcription factors, such as FOXO1 and ESR1, were identified as potential drivers of these transitions. Further cross-species comparisons revealed strong conservation in cell types, composition, and gene expression networks between sheep and human developing ovaries. Leveraging these conserved features, we uncovered context-dependent (e.g., cell-type-specific, developmental-stage-specific) associations with human reproductive traits and diseases. These findings advance our understanding of ovarian development in sheep and reinforce their utility as translational models in reproductive biology and disease research.

The chicken is a valuable model for understanding fundamental biology and vertebrate evolution and is a major global source of nutrient-dense and lean protein. Despite being the first non-mammalian amniote to have its genome sequenced, a systematic characterization of functional variation on the chicken genome remains lacking. Here, we integrated bulk RNA sequencing (RNA-seq) data from 7,015 samples, single-cell RNA-seq data from 127,598 cells and 2,869 whole-genome sequences to present a pilot atlas of regulatory variants across 28 chicken tissues. This atlas reveals millions of regulatory effects on primary expression (protein-coding genes, long non-coding RNA and exons) and post-transcriptional modifications (alternative splicing and 3'-untranslated region alternative polyadenylation). We highlighted distinct molecular mechanisms underlying these regulatory variants, their context-dependent behavior and their utility in interpreting genome-wide associations for 39 chicken complex traits. Finally, our comparative analyses of gene regulation between chickens and mammals demonstrate how this resource can facilitate cross-species gene mapping of complex traits.

Dominant follicular development and atresia are governed by the proliferation of granulosa cells (GCs), a process influenced by the delicate balance between apoptosis and autophagy. Oxidative stress, a pivotal catalyst of GCs apoptosis, modulates gene expression through epigenetic mechanisms, including chromatin remodeling. Nevertheless, the regulatory mechanisms underpinning GCs functionality in relation to prolificacy remain inadequately elucidated. In this study, we discovered that the chromatin accessibility of nuclear receptor subfamily 1 group D member 1 (NR1D1) was markedly enhanced in dominant follicular GCs from low-prolificacy sheep, as evidenced by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), which correlated with elevated NR1D1 transcript levels. Remarkably, NR1D1 emerged as a novel regulator of follicular development, exhibiting heightened expression in dominant follicles. The overexpression of NR1D1 induced cell cycle arrest, autophagy activation, and mitochondrial dysfunction via the AMPK pathway, while its knockdown fostered GCs survival and functionality. Furthermore, NR1D1 inhibits the transcription of HSD17B12, thereby contributing to oxidative stress (ROS)-induced apoptosis, as demonstrated by CUT&Tag-qPCR and dual luciferase assays. The downregulation of HSD17B12 partially alleviated the effects of NR1D1 knockdown on GCs functionality. These findings indicate that NR1D1 orchestrates GCs proliferation and apoptosis through the suppression of HSD17B12 and the activation of the AMPK pathway, establishing NR1D1 as a novel transcription factor implicated in follicular development and ovarian function, with significant implications for prolificacy.

Characterizing the impact of genomic variants on genome function and ultimately complex traits in livestock is essential for the development of sustainable precision agriculture and comparative genomics. Here, as part of the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we present the pilot phase of the SheepGTEx resource through analyzing 6,761 RNA-sequencing samples of 51 primary tissues in a multi-breed population of sheep. We identify millions of regulatory variants associated with seven types of molecular phenotypes, and fine-map 322,467 primary and 113,968 non-primary effects, revealing a high degree of regulatory allelic heterogeneity. We systematically characterize the pleiotropic effects of these variants on molecular phenotypes, assess their context-specific regulatory patterns across tissues, breeds, sexes, and developmental stages, as well as explore their evolutionary constraints across mammals. Finally, we demonstrate the substantial potential of the SheepGTEx resource (https://sheepgtex.farmgtex.org), by providing examples of regulatory mechanisms underpinning 34 complex traits, population divergence between European and Asian breeds, and adaptive evolution in sheep over the past ten millennia.

Understanding the genetic characteristics of indigenous goat breeds is vital for their conservation and breeding. Haimen goats, native to China’s Yangtze River Delta, possess distinctive traits such as white hair, moderate growth rate, high-quality meat, and small body size. However, knowledge regarding the genetic structure and germplasm characteristics of Haimen goats remains limited. In this study, we performed 20× whole-genome resequencing of 90 goats (60 Haimen goats and 30 Boer goats) to identify single-nucleotide polymorphisms (SNPs) and insertions/deletions (Indels) associated with growth traits. Here, we analyzed population genetic structure and genome-wide selection signatures between the Haimen and Boer goats based on whole-genome resequencing data. The principal component analysis (PCA) and neighbor-joining (N-J) tree results demonstrated significant genetic differentiation between the Haimen and Boer goats. The nucleotide diversity (Pi) and linkage disequilibrium (LD) decay results indicated higher genomic diversity in the Haimen goat population. Furthermore, selective sweep analysis identified candidate genes associated with growth traits. These genes exhibited strong selection signatures and were related to body size (DONSON, BMPR1B, and EPHA5), muscle development (GART, VGLL3, MYH15), and fat metabolism (ADAMTS5, LRP6, XDH, CPT1A, and GPD1). We also identified growth-related candidate genes (NCOR1, DPP6, NOTCH2, and FGGY) specific to Haimen goats. Among these genes, pancreatic lipase-related protein 1 (PNLIPRP1) emerged as the primary candidate gene influencing growth phenotypes. Further analysis revealed that a 26 bp Indel in PNLIPRP1 increased its gene expression, suggesting that this Indel could serve as a molecular marker for early marker-assisted selection, potentially enhancing early growth in goats. These findings provide valuable molecular markers and candidate genes for improving growth traits in Haimen goat breeding.

BACKGROUND:The pituitary gland, a central regulator of the hypothalamic-pituitary-gonadal (HPG) axis, plays a pivotal role in reproductive efficiency by precisely controlling the secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Chromatin accessibility enables physical interactions between promoters and chromatin-binding factors to drive the gene expression. Despite this mechanistic insight, the chromatin accessibility landscape of the sheep pituitary and its functional implications for reproductive traits remain largely unexplored. To address this knowledge gap, we performed an integrated multi-omics analysis of ATAC-seq and RNA-seq profiling of pituitary from sheep with divergent fecundity phenotypes. RESULTS:We identified 1,567 differential accessibility regions (DARs) and 768 differentially expressed genes (DEGs). Functional enrichment analysis revealed that the DEGs were significantly associated with key signaling pathways, including neuroactive ligand-receptor interactions, the cAMP signaling pathway, and the calcium signaling pathway, suggesting their critical roles in pituitary-regulated reproductive functions. Based on integrative analysis of ATAC-seq and RNA-seq, we revealed several potentially key genes involved in gonadotropin secretion, such as CMKLR1, TAFA1, and PPP1R17. Furthermore, we identified novel transcription factors (TFs), including NR4A2 and MEF2, which may influence pituitary hormone secretion by modulating chromatin accessibility and gene expression. CONCLUSIONS:This study systematically delineated the gene expression and chromatin accessibility of the pituitary and identified some key regulatory genes associated with gonadotropin secretion in sheep. Our integrated multi-omics analysis identifies critical molecular markers that may contribute to the genetic improvement of reproductive efficiency in ovine species.

Sheep (Ovis aries) represent one of the most important livestock species for global animal protein and wool production. However, little is known about the genetic and biological basis of ovine phenotypes, particularly those with high economic value and environmental impact. Here, by integrating 1413 RNA sequencing (RNA-seq) samples from 51 distinct tissues across 14 developmental time points, representing early-prenatal, late-prenatal, neonatal, lamb, juvenile, adult, and elderly stages, we constructed a high-resolution Developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. Leveraging this resource to interpret genetic associations for 48 monogenic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birthweight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating genome-wide association study (GWAS) fine-mapping results with the sheep dGEA, we identified several candidate genes for complex traits in sheep, such as SOX9 for MSL, GNRHR for litter size at birth, and PRKDC for live weight. These results provide novel insights into the developmental and molecular architecture of ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.

Mycoplasma pneumonia is a chronic respiratory disease that seriously affects the health of sheep. To date, little information is available about the damage caused by Mycoplasma ovipneumoniae (MO) pneumonia to host lungs. Here, after sheep were infected with MO for 28 days, severe inflammatory reactions and pathological damage occurred. By using single-cell RNA sequencing (scRNA-seq), all the transcriptome changes in 11 cell types in sheep lung tissue were systematically analyzed, and the key biological processes regulating inflammation and immunity were identified. Moreover, we constructed both intercellular communication models and differential expression maps of key regulatory genes for each cell subgroup. We also specifically focused on the response of T cell subpopulations and neutrophils to MO infection. Long-term infection may affect an organism's immune response, inhibit intercellular communication, and highlight the important role of the cyclophilin A (CypA) and macrophage migration inhibitory factor (MIF) pathways in intercellular communication. Notably, MO infection decreased the toxicity of CD8 effector T cells and depleted regulatory T cells, thus inhibiting normal cell function. Subsequently, emphasis was placed on the important role of the neutrophil marker gene S100A9 in promoting neutrophil clearance of MO through activation of the ERK signaling pathway and reactive oxygen species (ROS) burst in vitro. These results contribute to understanding the progression of MO infection in the lungs and provide a rich database on the molecular basis of the response to different cell types in MO infection.

Wool plays an irreplaceable role in the lives of livestock and the textile industry. The variety of hair quality and shape leads to the diversity of its functions and applications, and the finer wool has a higher economic value. In this study, 10 coarse and 10 fine ordos fine wool sheep skin samples were collected for RNA-seq, and coarse and fine skin/hair follicle RNA-seq datasets of other five animal breeds were obtained from NCBI. Weighted gene co-expression network analysis showed that the common genes were clustered into eight modules. Similar gene expression patterns in sheep and rabbits with the same wool types, different gene expression patterns in animal species with different hair types, and brown modules were significantly correlated with species and breeds. GO and KEGG enrichment analyses showed that, most genes in the brown module associated with hair follicle development. Hence, gene expression patterns in skin tissues may determine hair morphology in animal. The analysis of differentially expressed genes revealed that 32 highly expressed candidate genes associated with the wool fineness of Ordos fine wool sheep. Among them, KAZALD1 (grey module), MYOC (brown module), C1QTNF6 (brown module), FOS (tan module), ITGAM, MX2, MX1, and IFI6 genes have been reported to be involved in the regulation of the hair follicle cycle or hair loss. Additionally, 12 genes, including KAZALD1, MYOC, C1QTNF6, and FOS, are differentially expressed across various animal breeds and species. The above results suggest that different sheep breeds share a similar molecular regulatory basis of wool fineness. Finally, the study provides a theoretical reference for molecular breeding of sheep breeds as well as for the investigation of the origin and evolution of animal hair.

Oxidative stress is a significant factor in the death of granulosa cells (GCs), leading to follicular atresia and consequently limiting the number of dominant follicles that can mature and ovulate within each follicular wave. Follicular fluid contains a diverse array of metabolites that play crucial roles in regulating GCs’ proliferation and oocyte maturation, which are essential for follicle development and female fertility. However, the mechanisms behind metabolite heterogeneity and its effects on GCs’ function remain poorly understood. Here, we identified elevated nicotinamide levels in the follicular fluid of high-prolificacy sheep, correlated with oxidative stress in GCs, by an integrated analysis. In vitro experiments demonstrated that supplementation with β-nicotinamide mononucleotide (NMN) significantly increased the levels of nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) in GCs. NMN treatment effectively reduced Lipopolysaccharide (LPS)-induced apoptosis and mitigated mitochondrial dysfunction, while also decreasing the production of reactive oxygen species (ROS), thereby enhancing the activity of the antioxidant defense system. Importantly, NMN treatment improved the impairments in steroid hormone levels induced by LPS. Mechanistically, the protective effects of NMN against GCs function were mediated via the AMPK/mTOR pathway. Collectively, our findings elucidate the metabolic characteristics associated with sheep prolificacy and demonstrate that NMN effectively protects GCs from LPS-induced dysfunction and enhances ovarian responsiveness via the AMPK/mTOR pathway. These findings also position NMN as a potential novel metabolic biomarker in enhancing ovarian function.

Spermatogenesis is a complex process intricately regulated by the hypothalamic-pituitary-testis (HPT) axis. However, research on the regulatory factors governing the HPT axis remains limited. This study addresses this gap by conducting a comprehensive analysis of transcriptomes from the pituitary and testis tissues across various developmental stages, encompassing embryonic day (E120), neonatal period (P0), pre-puberty (P90), and post-puberty day (P270). Utilizing edgeR and WGCNA, we identified stage-specific genes in both the pituitary and testis throughout the four developmental stages. Notably, 380, 242, 34, and 479 stage-specific genes were identified in the pituitary, while 886, 297, 201, and 3,678 genes were identified in the testis. Subsequent analyses unveiled associations between these stage-specific genes and crucial pathways such as the cAMP signaling pathway, GnRH secretion, and male gamete generation. Furthermore, leveraging single-cell data from the pituitary and testis, we identified some signaling pathways involving BMP, HGF, IGF, and TGF-β, highlighting mutual regulation between the pituitary and testis at different developmental stages. This study sheds light on the pivotal role of the pituitary-testis axis in the reproductive process of sheep across four distinct developmental stages. Additionally, it delves into the intricate regulatory networks governing reproduction, offering novel insights into the dynamics of the pituitary-testis axis within the reproductive system.

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

Sheep (Ovis aries) represents one of the most important livestock species for animal protein and wool production worldwide. However, little is known about the genetic and biological basis of ovine phenotypes, particularly for those of high economic value and environmental impact. Here, by generating and integrating 1,413 RNA-seq samples from 51 distinct tissues across 14 developmental time points, representing early prenatal, late prenatal, neonate, lamb, juvenile, adult, and elderly stages, we built a high-resolution developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. When harnessing this resource for interpreting genomic associations of 48 monogenetic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birth weight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating fine-mapping results and the sheep dGEA, we identified several key genes associated with complex traits in sheep, such as SOX9 (associated with MSL), GNRHR (associated with litter size at birth), and PRKDC (associated with live weight). These results provide novel insights into the gene regulatory and developmental architecture underlying ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding. ### Competing Interest Statement The authors have declared no competing interest.

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.

Background The adaptive evolution of plateau indigenous animals is a current research focus. However, phenotypic adaptation is complex and may involve the interactions between multiple genes or pathways, many of which remain unclear. As a kind of livestock with important economic value, cashmere goat has a high ability of plateau adaptation, which provides us with good materials for studying the molecular regulation mechanism of animal plateau adaptation. Results In this study, 32 Jiangnan (J) and 32 Tibetan (T) cashmere goats were sequenced at an average of 10. Phylogenetic, population structure, and linkage disequilibrium analyses showed that natural selection or domestication has resulted in obvious differences in genome structure between the two breeds. Subsequently, 553 J vs. T and 608 T vs. J potential selected genes (PSGs) were screened. These PSGs showed potential relationships with various phenotypes, including myocardial development and activity ( LOC106502520 , ATP2A2 , LOC102181869 , LOC106502520 , MYL2 , ISL1 , and LOC102181869 genes), pigmentation ( MITF and KITLG genes), hair follicles/hair growth ( YAP1 , POGLUT1 , AAK1 , HES1 , WNT1 , PRKAA1 , TNKS , WNT5A , VAX2 , RSPO4 , CSNK1G1, PHLPP2 , CHRM2 , PDGFRB , PRKAA1 , MAP2K1 , IRS1 , LPAR1 , PTEN , PRLR , IBSP , CCNE2 , CHAD , ITGB7 , TEK , JAK2 , and FGF21 genes), and carcinogenesis ( UBE2R2 , PIGU , DIABLO , NOL4L , STK3 , MAP4 , ADGRG1 , CDC25A , DSG3 , LEPR , PRKAA1 , IKBKB , and ABCG2 genes). Phenotypic analysis showed that Tibetan cashmere goats has finer cashmere than Jiangnan cashmere goats, which may allow cashmere goats to better adapt to the cold environment in the Tibetan plateau. Meanwhile, KRTs and KAPs expression in Jiangnan cashmere goat skin was significantly lower than in Tibetan cashmere goat. Conclusions The mutations in these PSGs maybe closely related to the plateau adaptation ability of cashmere goats. In addition, the expression differences of KRTs and KAPs may directly determine phenotypic differences in cashmere fineness between the two breeds. In conclusion, this study provide a reference for further studying plateau adaptive mechanism in animals and goat breeding.

Abstract Chicken is a valuable model for understanding fundamental biology and vertebrate evolution, as well as a major source of nutrient-dense and lean-protein-enriched food globally. Although it is the first non-mammalian amniote genome to be sequenced, the chicken genome still lacks a systematic characterization of functional variation. Here, through integrating bulk RNA-Seq of 7,015 samples, single-cell RNA-Seq of 127,598 cells and 2,869 whole-genome sequences, we presented an atlas of regulatory variants across 28 chicken tissues and 43 cell types, including millions of regulatory effects on primary expression (protein-coding genes, lncRNA and exon) and post-transcriptional modifications (alternative splicing and 3’ untranslated region alternative polyadenylation). We highlighted distinct molecular mechanisms underlying these regulatory variants and their context dependence and utility in interpreting genome-wide associations of 108 chicken complex traits. Finally, we illustrated lineage-specific features of gene regulation between chickens and mammals, and demonstrated how this resource can assist with cross-species gene mapping of complex traits.