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  • Springer Science and Business Media LLC  (10)
  • Liu, George E.  (10)
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  • Springer Science and Business Media LLC  (10)
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  • 1
    Online Resource
    Online Resource
    Functional annotation of the cattle genome through systematic discovery and characterization of chromatin states and butyrate-induced variations
    Springer Science and Business Media LLC ; 2019
    In:  BMC Biology Vol. 17, No. 1 ( 2019-12)
    Details
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 1741-7007
    URL: Article
    DOI: 10.1186/s12915-019-0687-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2133020-7
    SSG: 12
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  • 2
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    Comparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patterns
    Springer Science and Business Media LLC ; 2020
    In:  BMC Biology Vol. 18, No. 1 ( 2020-12)
    Details
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 18, No. 1 ( 2020-12)
    Abstract: Efforts to improve animal health, and understand genetic bases for production, may benefit from a comprehensive analysis of animal genomes and epigenomes. Although DNA methylation has been well studied in humans and other model species, its distribution patterns and regulatory impacts in cattle are still largely unknown. Here, we present the largest collection of cattle DNA methylation epigenomic data to date. Results Using Holstein cattle, we generated 29 whole genome bisulfite sequencing (WGBS) datasets for 16 tissues, 47 corresponding RNA-seq datasets, and 2 whole genome sequencing datasets. We did read mapping and DNA methylation calling based on two different cattle assemblies, demonstrating the high quality of the long-read-based assembly markedly improved DNA methylation results. We observed large differences across cattle tissues in the methylation patterns of global CpG sites, partially methylated domains (PMDs), hypomethylated regions (HMRs), CG islands (CGIs), and common repeats. We detected that each tissue had a distinct set of PMDs, which showed tissue-specific patterns. Similar to human PMD, cattle PMDs were often linked to a general decrease of gene expression and a decrease in active histone marks and related to long-range chromatin organizations, like topologically associated domains (TADs). We tested a classification of the HMRs based on their distributions relative to transcription start sites (TSSs) and detected tissue-specific TSS-HMRs and genes that showed strong tissue effects. When performing cross-species comparisons of paired genes (two opposite strand genes with their TSS located in the same HMR), we found out they were more consistently co-expressed among human, mouse, sheep, goat, yak, pig, and chicken, but showed lower consistent ratios in more divergent species. We further used these WGBS data to detect 50,023 experimentally supported CGIs across bovine tissues and found that they might function as a guard against C-to-T mutations for TSS-HMRs. Although common repeats were often heavily methylated, some young Bov-A2 repeats were hypomethylated in sperm and could affect the promoter structures by exposing potential transcription factor binding sites. Conclusions This study provides a comprehensive resource for bovine epigenomic research and enables new discoveries about DNA methylation and its role in complex traits.
    Type of Medium: Online Resource
    ISSN: 1741-7007
    URL: Article
    DOI: 10.1186/s12915-020-00793-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2133020-7
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  • 3
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    Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle
    Springer Science and Business Media LLC ; 2019
    In:  BMC Genomics Vol. 20, No. 1 ( 2019-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2019-12)
    Abstract: DNA methylation has been shown to be involved in many biological processes, including X chromosome inactivation in females, paternal genomic imprinting, and others. Results Based on the correlation patterns of methylation levels of neighboring CpG sites among 28 sperm whole genome bisulfite sequencing (WGBS) data (486 × coverage), we obtained 31,272 methylation haplotype blocks (MHBs). Among them, we defined conserved methylated regions (CMRs), variably methylated regions (VMRs) and highly variably methylated regions (HVMRs) among individuals, and showed that HVMRs might play roles in transcriptional regulation and function in complex traits variation and adaptive evolution by integrating evidence from traditional and molecular quantitative trait loci (QTL), and selection signatures. Using a weighted correlation network analysis (WGCNA), we also detected a co-regulated module of HVMRs that was significantly associated with reproduction traits, and enriched for glycosyltransferase genes, which play critical roles in spermatogenesis and fertilization. Additionally, we identified 46 VMRs significantly associated with reproduction traits, nine of which were regulated by cis-SNPs, implying the possible intrinsic relationships among genomic variations, DNA methylation, and phenotypes. These significant VMRs were co-localized (± 10 kb) with genes related to sperm motility and reproduction, including ZFP36L1 , CRISP2 and HGF . We provided further evidence that rs109326022 within a predominant QTL on BTA18 might influence the reproduction traits through regulating the methylation level of nearby genes JOSD2 and ASPDH in sperm. Conclusion In summary, our results demonstrated associations of sperm DNA methylation with reproduction traits, highlighting the potential of epigenomic information in genomic improvement programs for cattle.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/s12864-019-6228-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2041499-7
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  • 4
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    Towards the detection of copy number variation from single sperm sequencing in cattle
    Springer Science and Business Media LLC ; 2022
    In:  BMC Genomics Vol. 23, No. 1 ( 2022-03-17)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-03-17)
    Abstract: Copy number variation (CNV) has been routinely studied using bulk-cell sequencing. However, CNV is not well studied on the single-cell level except for humans and a few model organisms. Results We sequenced 143 single sperms of two Holstein bulls, from which we predicted CNV events using 14 single sperms with deep sequencing. We then compared the CNV results derived from single sperms with the bulk-cell sequencing of one bull’s family trio of diploid genomes. As a known CNV hotspot, segmental duplications were also predicted using the bovine ARS-UCD1.2 genome. Although the trio CNVs validated only some single sperm CNVs, they still showed a distal chromosomal distribution pattern and significant associations with segmental duplications and satellite repeats. Conclusion Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for CNV detection using single cell sequencing data.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/s12864-022-08441-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041499-7
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  • 5
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    Single-cell transcriptomic and chromatin accessibility analyses of dairy cattle peripheral blood mononuclear cells and their responses to lipopolysaccharide
    Springer Science and Business Media LLC ; 2022
    In:  BMC Genomics Vol. 23, No. 1 ( 2022-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: Gram-negative bacteria are important pathogens in cattle, causing severe infectious diseases, including mastitis. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and crucial mediators of chronic inflammation in cattle. LPS modulations of bovine immune responses have been studied before. However, the single-cell transcriptomic and chromatin accessibility analyses of bovine peripheral blood mononuclear cells (PBMCs) and their responses to LPS stimulation were never reported. Results We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) in bovine PBMCs before and after LPS treatment and demonstrated that seven major cell types, which included CD4 T cells, CD8 T cells, and B cells, monocytes, natural killer cells, innate lymphoid cells, and dendritic cells. Bioinformatic analyses indicated that LPS could increase PBMC cell cycle progression, cellular differentiation, and chromatin accessibility. Gene analyses further showed significant changes in differential expression, transcription factor binding site, gene ontology, and regulatory interactions during the PBMC responses to LPS. Consistent with the findings of previous studies, LPS induced activation of monocytes and dendritic cells, likely through their upregulated TLR4 receptor. NF-κB was observed to be activated by LPS and an increased transcription of an array of pro-inflammatory cytokines, in agreement that NF-κB is an LPS-responsive regulator of innate immune responses. In addition, by integrating LPS-induced differentially expressed genes (DEGs) with large-scale GWAS of 45 complex traits in Holstein, we detected trait-relevant cell types. We found that selected DEGs were significantly associated with immune-relevant health, milk production, and body conformation traits. Conclusion This study provided the first scRNAseq and scATAC-seq data for cattle PBMCs and their responses to the LPS stimulation to the best of our knowledge. These results should also serve as valuable resources for the future study of the bovine immune system and open the door for discoveries about immune cell roles in complex traits like mastitis at single-cell resolution.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/s12864-022-08562-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041499-7
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  • 6
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    The single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells in Chinese holstein cattle
    Springer Science and Business Media LLC ; 2023
    In:  BMC Genomic Data Vol. 24, No. 1 ( 2023-08-07)
    Details
    In: BMC Genomic Data, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-08-07)
    Abstract: This study was performed in the frame of a more extensive study dedicated to the integrated analysis of the single-cell transcriptome and chromatin accessibility datasets of peripheral blood mononuclear cells (PBMCs) with a large-scale GWAS of 45 complex traits in Chinese Holstein cattle. Lipopolysaccharide (LPS) is a crucial mediator of chronic inflammation to modulate immune responses. PBMCs include primary T and B cells, natural killer (NK) cells, monocytes (Mono), and dendritic cells (DC). How LPS stimulates PBMCs at the single-cell level in dairy cattle remains largely unknown. Data description We sequenced 30,756 estimated single cells and mapped 26,141 of them (96.05%) with approximately 60,075 mapped reads per cell after quality control for four whole-blood treatments (no, 2 h, 4 h, and 8 h LPS) by single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq). Finally, 7,107 (no), 9,174 (2 h), 6,741 (4 h), and 3,119 (8 h) cells were generated with ~ 15,000 total genes in the whole population. Therefore, the single-cell transcriptome and chromatin accessibility datasets in this study enable a further understanding of the cell types and functions of PBMCs and their responses to LPS stimulation in vitro.
    Type of Medium: Online Resource
    ISSN: 2730-6844
    URL: Article
    DOI: 10.1186/s12863-023-01139-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041497-3
    detail.hit.zdb_id: 3058779-7
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  • 7
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    Investigation of rumen long noncoding RNA before and after weaning in cattle
    Springer Science and Business Media LLC ; 2022
    In:  BMC Genomics Vol. 23, No. 1 ( 2022-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: This study aimed to identify long non-coding RNA (lncRNA) from the rumen tissue in dairy cattle, explore their features including expression and conservation levels, and reveal potential links between lncRNA and complex traits that may indicate important functional impacts of rumen lncRNA during the transition to the weaning period. Results A total of six cattle rumen samples were taken with three replicates from before and after weaning periods, respectively. Total RNAs were extracted and sequenced with lncRNA discovered based on size, coding potential, sequence homology, and known protein domains. As a result, 404 and 234 rumen lncRNAs were identified before and after weaning, respectively. However, only nine of them were shared under two conditions, with 395 lncRNAs found only in pre-weaning tissues and 225 only in post-weaning samples. Interestingly, none of the nine common lncRNAs were differentially expressed between the two weaning conditions. LncRNA averaged shorter length, lower expression, and lower conservation scores than the genome overall, which is consistent with general lncRNA characteristics. By integrating rumen lncRNA before and after weaning with large-scale GWAS results in cattle, we reported significant enrichment of both pre- and after-weaning lncRNA with traits of economic importance including production, reproduction, health, and body conformation phenotypes. Conclusions The majority of rumen lncRNAs are uniquely expressed in one of the two weaning conditions, indicating a functional role of lncRNA in rumen development and transition of weaning. Notably, both pre- and post-weaning lncRNA showed significant enrichment with a variety of complex traits in dairy cattle, suggesting the importance of rumen lncRNA for cattle performance in the adult stage. These relationships should be further investigated to better understand the specific roles lncRNAs are playing in rumen development and cow performance.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/s12864-022-08758-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041499-7
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  • 8
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    Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep
    Springer Science and Business Media LLC ; 2021
    In:  BMC Biology Vol. 19, No. 1 ( 2021-12)
    Details
    In: BMC Biology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: Characterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin. Results We analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g. SPHK1 , GHR , PPP1R27 , CSRP2 , EEF1A2 , and PTPN1 ) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans. Conclusions Our study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.
    Type of Medium: Online Resource
    ISSN: 1741-7007
    URL: Article
    DOI: 10.1186/s12915-021-01127-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2133020-7
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  • 9
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    Genome-wide recombination map construction from single sperm sequencing in cattle
    Springer Science and Business Media LLC ; 2022
    In:  BMC Genomics Vol. 23, No. 1 ( 2022-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: Meiotic recombination is one of the important phenomena contributing to gamete genome diversity. However, except for human and a few model organisms, it is not well studied in livestock, including cattle. Results To investigate their distributions in the cattle sperm genome, we sequenced 143 single sperms from two Holstein bulls. We mapped meiotic recombination events at high resolution based on phased heterozygous single nucleotide polymorphism (SNP). In the absence of evolutionary selection pressure in fertilization and survival, recombination events in sperm are enriched near distal chromosomal ends, revealing that such a pattern is intrinsic to the molecular mechanism of meiosis. Furthermore, we further validated these findings in single sperms with results derived from sequencing its family trio of diploid genomes and our previous studies of recombination in cattle. Conclusions To our knowledge, this is the first large-scale single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of recombination, genome instability, and male infertility.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/s12864-022-08415-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 10
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    Comparative transcriptome in large-scale human and cattle populations
    Springer Science and Business Media LLC ; 2022
    In:  Genome Biology Vol. 23, No. 1 ( 2022-08-22)
    Details
    In: Genome Biology, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-08-22)
    Abstract: Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. Results Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. Conclusions In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.
    Type of Medium: Online Resource
    ISSN: 1474-760X
    URL: Article
    DOI: 10.1186/s13059-022-02745-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2040529-7
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