Biology subjects

GUAN, D.

Publications and source records attributed to GUAN, D..

4 recordsLinked to original sources

bioRxiv2026

The enhanced multi-tissue atlas of regulatory effects in cattle

Cattle are integral to global food security, yet the molecular architecture of their complex traits remains poorly understood. Here, we present the Cattle Genotype-Tissue Expression (CattleGTEx) Phase 1 resource (https://cattlegtex.farmgtex.org/), a substantial expansion of the pilot study. By leveraging 12,422 RNA-seq profiles across 43 tissues and 82 breeds, we characterized 433,972 primary and 161,428 non-primary regulatory effects spanning seven molecular phenotypes. This high-resolution atlas resolves 75% of GWAS signals for 44 complex traits, significantly addressing the "missing regulation" in livestock. We propose a genetic regulatory model demonstrating how variants across multiple biological layers interact with specific biological contexts to shape phenotypic variation. Furthermore, CattleGTEx elucidates mechanisms underlying adaptive evolution between Bos taurus and Bos indicus, as well as artificial selection in dairy and beef breeds. Finally, by mapping evolutionary constraints on these regulatory effects, we demonstrate the translational value of this resource for prioritizing causal variants in human complex diseases. Together, Phase 1 of CattleGTEx provides a transformative framework for functional genomics, precision breeding, and comparative genetics.

genetics↗

bioRxiv2026

Sex-specific Genetic Regulatory Effects in Chickens

Sexual dimorphism is a defining vertebrate feature, yet its sex-specific molecular architecture remains poorly understood. Here we established a sex-balanced, uniformly reared chicken cohort to map this landscape, integrating individual whole-genome sequencing with 7,969 bulk and 779,380 single nucleus transcriptomes across 32 tissues from 280 birds. We identified 495,098 independent expression quantitative trait loci for 20,194 genes, including 10,937 loci modulated by cell-type composition. Notably, 340 genes were regulated by 449 loci in a sex-dependent manner, significantly enrichment in endocrine tissues like adipose and the adrenal gland. Furthermore, we fine-mapped 1,219 structural variants, demonstrating their unique roles to tissue- and sex-specific expression beyond SNPs. Ultimately, we showed the utility of these regulatory effects in elucidating the molecular basis of metabolism and complex traits in both chickens and humans. This comprehensive atlas of regulatory effects provides profound insights into the genomic and molecular basis of sexual dimorphism in vertebrates.

genomics↗

bioRxiv2025

An atlas of cell type specific regulatory effects in cattle

Understanding the genetic and molecular architecture of complex traits and artificial selection is crucial for advancing sustainable precision breeding in cattle and other livestock. Yet, how genetic variation affects cellular gene expression remains elusive in cattle. Here, by integrating 8,866 bulk RNA-seq samples and 999,192 single cells of 81 cell types in 22 bovine tissues, we presented a comprehensive atlas of regulatory variants at the cell type resolution in cattle. By colocalizing with bulk-tissue expression quantitative trait loci (beQTL), we detected 57,043 novel cell-type stratified eQTL and cell-type/state interaction eQTL in 18,153 genes, which also exhibited a stronger tissue/cell-type specificity than beQTL. By examining genome-wide associations (GWAS) of 44 complex traits, these cell-resolved eQTL were colocalized with 505 (24%) additional GWAS loci compared to beQTL. Through integrating this resource with selection signatures between dairy and beef cattle, we provided tissue/cell-specific regulatory insights into cattle breeding. Overall, the current atlas of cell-type-specific regulatory variants will serve as an invaluable resource for cattle genomics and selective breeding.

genetics↗

bioRxiv2025

Potential Mechanisms Underlying Kaempferol-Promoted Osteoblast Proliferation and Osteogenic Differentiation: A Network Pharmacology and Experimental Validation Study

BackgroundOsteoporosis (OP) manifests primarily in middle-aged and elderly individuals, representing an age-related condition characterised by diminished bone mass and alterations in bone tissue structure, potentially resulting in fractures and compromising the patients quality of life. The potential of kaempferol to modulate osteogenic differentiation, enhance bone metabolism, and potentially offer therapeutic benefits in OP cases is of particular interest. This study, employing a combination of network pharmacology and experimental verification, investigated the underlying mechanisms by which kaempferol stimulates the proliferation and osteogenic differentiation of mouse embryonic osteoblast precursor cells MC3T3-E1 subclone 14 through the PI3K/AKT signalling pathway. The findings provide a rational foundation for the potential of kaempferol to promote osteogenesis and enhance the treatment of OP. MethodsThe present study identified target genes regulated by kaempferol during osteogenesis and differentiation using network pharmacology. To this end, a protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and molecular docking were performed.The cytotoxicity of kaempferol was assessed using the CCK-8 method and the cell clone method in the cell detection section.The macroscopic regulatory mechanism of kaempferol in osteogenic differentiation was studied using alkaline phosphatase staining, activity assay, Alizarin Red staining, and calcium quantification{o} Furthermore, real-time quantitative polymerase chain reaction (RT qPCR) and Western blot methods were employed to detect the microscopic expression differences of mRNA and protein related to the PI3K/AKT signalling pathway.The present study identified target genes regulated by kaempferol during osteogenesis and differentiation using network pharmacology. To this end, a protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and molecular docking were performed. ResultsA total of 203 target genes regulated by kaempferol were identified during osteogenic differentiation, with the majority of these genes being associated with biological processes related to cell proliferation and regulation.Four of these target genes act on the PI3K/AKT signalling pathway and show good interactions with kaempferol. Furthermore, kaempferol (5 M, 10 M) has been shown to enhance the vitality and proliferation of MC3T3-E1 Subclone 14 cells, as well as to increase alkaline phosphatase activity and calcium deposition. Furthermore, kaempferol (5 M, 10 M) has been observed to upregulate the mRNA expression of phosphoinositide 3-kinase (Pi3k), {beta}-catenin, Myc proto-oncogene protein (c-Myc), and cyclin D1 in MC3T3-E1 Subclone. 14 cells, and promotes the phosphorylation of PI3K, serine/threonine protein kinase AKT (AKT1) and glycogen synthase kinase, as well as the phosphorylation of glycogen synthase kinase-3{beta} (GSK3{beta}) (p < 0.05), thereby upregulating the expression of {beta}-catenin, C-MYC and CYCLIN D1 proteins and increasing the levels of p-PI3K/PI3K, p-AKT1/AKT1 and p-GSK3{beta}/GSK3{beta} levels, thereby promoting osteogenic differentiation of MC3T3-E1 Subclone 14. ConclusionKaempferol has been demonstrated to have the capacity to significantly promote the osteogenic differentiation of MC3T3-E1 Subclone 14. This process is thought to be achieved by regulating the PI3K/AKT signalling pathway and affecting the expression of osteogenic-related genes. It has been shown to have a preventive and therapeutic effect on the occurrence and development of osteoporosis.

cell biology↗