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Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

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Journal of animal Science and Biotechnology 2024年第1期15卷 53-67页

作者： Xiaoli Guo Qianqian Zhou Jiaming Jin Fangren Lan Chaoliang Wen Junying Li Ning Yang Congjiao Sun National Engineering Laboratory for animal breeding and Key Laboratory of animal genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsChina Agricultural UniversityBeijing 100193China

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the ch

关键词： Acetylation Cholesterol metabolism Hepatic steatosis Laying hens Multiomics

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Single‑cell sequencing reveals the reproductive variations between primiparous and multiparous Hu ewes

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Journal of animal Science and Biotechnology 2024年第2期15卷 614-631页

作者： Ting Ge Yifan Wen Bo Li Xiaoyu Huang Shaohua Jiang Enping Zhang Key Laboratory of animal genetics Breeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China

Background In the modern sheep production systems,the reproductive performance of ewes determines the economic profitability of farming.Revealing the genetic mechanisms underlying differences in the litter size is important for the selection and breeding of highly prolific ewes.Hu sheep,a high-quality Chinese sheep breed,is known for its high fecundity and is often used as a model to study prolificacy traits.In the current study,animals were divided into two groups according to their delivery rates in three consecutive lambing seasons(namely,the high and low reproductive groups with≥3 lambs and one lamb per season,n=3,respectively).The ewes were slaughtered within 12 h of estrus,and unilateral ovarian tissues were collected and analyzed by 10×Genomics single-cell RNA sequencing.Results A total of 5 types of somatic cells were identified and corresponding expression profiles were mapped in the ovaries of each group.Noticeably,the differences in the ovary somatic cell expression profiles between the high and low reproductive groups were mainly clustered in the granulosa cells.Furthermore,four granulosa cell subtypes were identified.GeneSwitches analysis revealed that the abundance of JPH1 expression and the reduction of LOC101112291 expression could lead to different evolutionary directions of the granulosa cells.Additionally,the expression levels of FTH1 and FTL in mural granulosa cells of the highly reproductive group were significantly higher.These genes inhibit necroptosis and ferroptosis of mural granulosa cells,which helps prevent follicular atresia.Conclusions This study provides insights into the molecular mechanisms underlying the high fecundity of Hu sheep.The differences in gene expression profiles,particularly in the granulosa cells,suggest that these cells play a critical role in female prolificacy.The findings also highlight the importance of genes such as JPH1,LOC101112291,FTH1,and FTL in regulating granulosa cell function and follicular development.

关键词： Granulosa cells Hu sheep Lambing number Ovarian somatic cells Single-cell RNA sequencing

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Hi-Tag:a simple and efficient method for identifying protein-mediated long-range chromatin interactions with low cell numbers

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Science China(Life Sciences) 2024年第5期67卷 1027-1034页

作者： Xiaolong Qi Lu Zhang Qiulin Zhao Peng Zhou Sai Xian Zhang Jingjin Li Zhuqing Zheng Yue Xiang Xueting Dai Zhe Jin Yaobang Jian Xinyun Li Liangliang Fu Shuhong Zhao Key Lab of Agricultural animal genetics Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of AgricultureCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China The Cooperative Innovation Center for Sustainable Pig Production Wuhan 430070China Hubei Hongshan Laboratory Frontiers Science Center for Animal Breeding and Sustainable ProductionWuhan 430070China

Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation.However,these techniques require complex experimental procedures and millions of cells per experiment,which limits their widespread application in life science research.Here,we develop a novel method,Hi-Tag,that identifies high-resolution,long-range chromatin interactions through transposase tagmentation and chromatin proximity ligation(with a phosphorothioate-modified linker).Hi-Tag can be implemented using as few as 100,000 cells,involving simple experimental procedures that can be completed within 1.5 days.Meanwhile,Hi-Tag is capable of using its own data to identify the binding sites of specific proteins,based on which,it can acquire accurate interaction information.Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies,particularly in the context of limited cell availability.

关键词： Hi-Tag chromatin interactions transposase tagmentation chromatin proximity ligation low cell numbers

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A cell transcriptomic profile p ovides insights into adipocytes of porcine mammary gland across development

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Journal of animal Science and Biotechnology 2024年第1期15卷 182-200页

作者： Yongliang Fan Long Jin Zhiping He Tiantian Wei Tingting Luo Jiaman Zhang Can Liu Changjiu Dai Chao A Yan Liang Xuan Tao Xuebin Lv Yiren Gu Mingzhou Li State Key Laboratory of Swine and Poultry breeding Industry College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China Key Laboratory of Qinghai‑Tibetan Plateau animal Genetic Resource Reservation and Utilization Southwest Minzu UniversityChengdu 610041China animal breeding and genetics Key Laboratory of Sichuan Province Sichuan Animal Science AcademyChengdu 610000China

Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes.Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells t

关键词： Adipocytes Cell–cell interaction Development Mammary gland snRNA-seq

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KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

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Science China(Life Sciences) 2024年第1期67卷 96-112页

作者： Wei Zhu Guowei Bu Ruifeng Hu Jixiang Zhang Lianyong Qiao Kai Zhou Tingting Wang Qiao Li Jingjing Zhang Linhui Wu Yali Xie Taotao Hu Shichun Yang Jiaqi Guan Xiaoyu Chu Juanjuan Shi Xia Zhang Falong Lu Xin Liu Yi-Liang Miao institute of Stem Cell and Regenerative Biology College of Animal Science and Veterinary MedicineHuazhong Agricultural UniversityWuhan 430070China Key Laboratory of Agricultural animal genetics Breeding and Reproduction(Huazhong Agricultural University)Ministry of EducationWuhan 430070China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyInnovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China Frontiers Science Center for animal breeding and Sustainable Production Huazhong Agricultural UniversityWuhan 430070China Hubei Hongshan Laboratory Wuhan 430070China

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos.Current studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear.By employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.Our data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early embryos.Knocking down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine blastocysts.Furthermore,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine embryos.In addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this process.Taken together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.

关键词： porcine embryos liDNase-seq chromatin accessibility KLF4 mitochondrion lipid droplets

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Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing Zhang Yaning Hu Piao Zhu Hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering Laboratory for animal breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial Key Laboratory of animal Molecular Design and Precise breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China State Key Laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient times.However,the knowledge of their migration routes and genetic relationships is still poorly understood.To investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 BP.The combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern Asia.At least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 BP.Overall,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

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miR-24-3p promotes proliferation and inhibits apoptosis of porcine granulosa cells by targeting P27

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Journal of Integrative Agriculture 2024年第4期23卷 1315-1328页

作者： Shengjie Shi Lutong Zhang Liguang Wang Huan Yuan Haowei Sun Mielie Madaniyati Chuanjiang Cai Weijun Pang Lei Gao Guiyan Chu College of animal Science and Technology Northwest A&F UniversityYangling 712100China Key Laboratory of animal genetics Breeding and Reproduction of Shaanxi ProvinceYangling 712100China

Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.

关键词： miR-24-3p granulosa cells proliferation apoptosis

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Diarrhea induced by insufficient fat absorption in weaned piglets:Causes and nutrition regulation

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animal Nutrition 2024年第1期16卷 299-305页

作者： Yuying Li Pengjun Shi Kang Yao Qian Lin Mansheng Wang Zhenping Hou Wenjie Tang Hui Diao institute of Bast Fiber Crops Chinese Academy of Agricultural Sciences institute of Subtropical Agriculture Chinese Academy of Sciences Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process animal breeding and genetics Key Laboratory of Sichuan Province Livestock and Poultry Biological Products Key Laboratory of Sichuan Province Sichuan Animal Science Academy Sichuan Animtech Feed Co. Ltd

Fat is one of the three macronutrients and a significant energy source for piglets. It plays a positive role in maintaining intestinal health and improving production performance. During the weaning period,physiological, stress and diet-related factors influence the absorption of fat in piglets, leading to damage to the intestinal barrier, diarrhea and even death. Signaling pathways, such as fatty acid translocase(CD36), pregnane X receptor(PXR), and AMP-dependent protein kinase(AMPK), are responsible for regulating intestinal fat uptake and maintaining intestinal barrier function. Therefore, this review mainly elaborates on the reasons for diarrhea induced by insufficient fat absorption and related signaling pathways in weaned-piglets, with an emphasis on the intestinal fat absorption disorder. Moreover, we focus on introducing nutritional strategies that can promote intestinal fat absorption in piglets with insufficient fat absorption-related diarrhea, such as lipase, amino acids, and probiotics.

关键词： Weaned piglet Diarrhea Fat absorption Nutrient regulation

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Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

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Journal of animal Science and Biotechnology 2024年第2期15卷 519-534页

作者： Changming Hong Yujian Huang Shuting Cao Li Wang Xuefen Yang Shenglan Hu Kaiguo Gao Zongyong Jiang Hao Xiao State Key Laboratory of Swine and Poultry breeding Industry Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South ChinaGuangdong Public Laboratory of Animal Breeding and NutritionGuangdong Provincial Key Laboratory of Animal Breeding and NutritionMaoming BranchGuangdong Laboratory for Lingnan Modern AgricultureGuangzhouChina institute of animal Science Guangdong Academy of Agricultural Sciences1 Dafeng 1st StreetGuangzhou 510640China

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

关键词： Accurate models Dose Nutritional strategies Oxidative stress Swine

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Associations of genome-wide structural variations with phenotypic differences in cross-bred Eurasian pigs

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Journal of animal Science and Biotechnology 2024年第1期15卷 68-87页

作者： Wencheng Zong Jinbu Wang Runze Zhao Naiqi Niu Yanfang Su Ziping Hu Xin Liu Xinhua Hou Ligang Wang Lixian Wang Longchao Zhang State Key Laboratory of animal Biotech breeding Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193China College of animal Science Shanxi Agricultural UniversityJinzhong 030801China College of animal Science and Technology Qingdao Agricultural UniversityQingdao 266109China

Background During approximately 10,000 years of domestication and selection,a large number of structural variations(SVs)have emerged in the genome of pig breeds,profoundly influencing their phenotypes and the ability to adapt to the local environment.SVs(≥50 bp)are widely distributed in the genome,mainly in the form of insertion(INS),mobile element insertion(MEI),deletion(DEL),duplication(DUP),inversion(INV),and translocation(TRA).While studies have investigated the SVs in pig genomes,genome-wide association studies(GWAS)-based on SVs have been rarely conducted.Results Here,we obtained a high-quality SV map containing 123,151 SVs from 15 Large White and 15 Min pigs through integrating the power of several SV tools,with 53.95%of the SVs being reported for the first time.These high-quality SVs were used to recover the population genetic structure,confirming the accuracy of genotyping.Potential functional SV loci were then identified based on positional effects and breed stratification.Finally,GWAS were performed for 36 traits by genotyping the screened potential causal loci in the F2 population according to their corresponding genomic positions.We identified a large number of loci involved in 8 carcass traits and 6 skeletal traits on chromosome 7,with FKBP5 containing the most significant SV locus for almost all traits.In addition,we found several significant loci in intramuscular fat,abdominal circumference,heart weight,and liver weight,etc.Conclusions We constructed a high-quality SV map using high-coverage sequencing data and then analyzed them by performing GWAS for 25 carcass traits,7 skeletal traits,and 4 meat quality traits to determine that SVs may affect body size between European and Chinese pig breeds.

关键词： Body size GWAS Pig Skeleton Structural variations

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