Publications by authors named "Keren Long"

Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological processes by binding to the 3' untranslated regions of mRNAs.

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Triglyceride (TG) metabolism is a complex and highly coordinated biological process regulated by a series of genes, and its dysregulation can lead to the occurrence of disorders in lipid metabolism. However, the transcriptional regulatory mechanisms of crucial genes in TG metabolism mediated by enhancer-promoter interactions remain elusive. Here, we identified candidate enhancers regulating the Agpat2, Dgat1, Dgat2, Pnpla2, and Lipe genes in 3T3-L1 adipocytes by integrating epigenomic data (H3K27ac, H3K4me1, and DHS-seq) with chromatin three-dimensional interaction data.

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Olfactory receptors (ORs) are members of the transmembrane G protein-coupled receptor superfamily, playing a crucial role in odor recognition, which further mediates crucial biological processes in mammals. In sows, androstenone can trigger sexual behaviors through olfaction, but the underlying mechanism remains to be explored. To efficiently and accurately screen pig olfactory receptors responding to androstenone and the key structure determinant, we adapted the high-throughput RNA-seq strategy to screen the altered genes upon androstenone treatment in the olfactory epithelium of pigs, yielding 1397 downregulated genes.

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Introduction: Despite of numerous studies of the placenta, some molecular and cellular characteristics, particularly the relationship among different cell types, have not been well understood. We aim to investigate the basic and intricate details of cellular and molecular elements in early and late phase placentas to gain better understanding of the immune regulation of human reproductive process.

Methods: A novel combination of techniques of spatial transcriptomics(ST), multiple immunohistochemistry, and a dual labeling combining immunohistochemistry and (fluorescence in situ hybridization) FISH on normal and ectopic pregnancy and animal models was employed to investigate the placenta at tissue, cell, protein and molecular levels and to trace the fetal and maternal origin of every cell in early and late placentas.

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Porcine latissimus dorsi muscle (LDM) is a crucial source of pork products. Meat quality indicators, such as the proportion of muscle fibers and intramuscular fat (IMF) deposition, vary during the growth and development of pigs. Numerous studies have highlighted the heterogeneous nature of skeletal muscle, with phenotypic differences reflecting variations in cellular composition and transcriptional profiles.

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Article Synopsis
  • G0s2 is an inhibitor of adipose triglyceride lipase (ATGL), influencing triglyceride mobilization in fat and liver cells, and is linked to metabolic disorders like obesity and NAFLD.
  • Researchers discovered three active enhancers of the G0s2 gene in adipocytes, which play a crucial role in its expression and lipid droplet formation.
  • Further analyses showed that specific transcription factors, particularly PPARG and RXRA, regulate one of these enhancers (G0S2-En5), impacting pathways related to lipid metabolism.
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  • - Angiogenesis, crucial for processes like embryonic development and cancer, is influenced by long noncoding RNAs (lncRNAs), which regulate gene expression, including the lncRNA MYU that enhances prostate cancer and is upregulated in hypoxic conditions.
  • - The study focused on MYU's role in promoting angiogenesis in vascular endothelial cells under hypoxia, examining its impact on the expression of miR-23a-3p and interleukin-8 (IL-8) in human umbilical vein endothelial cells (HUVECs).
  • - Results showed that increased MYU levels and decreased miR-23a-3p led to enhanced proliferation, migration, and tube formation of H
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  • Commensal microbes play a vital role in the metabolism, growth, and immune function of hosts, but research in large animal models has been rare.
  • This study focused on the immune response of germ-free (GF) and specific-pathogen-free (SPF) piglets, revealing that SPF piglets have a more developed immune system than GF piglets, as shown by their larger spleen and increased immune cell presence.
  • RNA sequencing and quantitative PCR identified higher expression of immune-related genes and pathways in SPF piglets, highlighting the significant influence of commensal microbiota on immune tissue structure and overall immune function.
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  • MicroRNAs (miRNAs) are short, noncoding RNAs that play a crucial role in deciding cell fates, particularly in processes like adipogenic differentiation for developing white fat tissue.
  • This study identified 78 miRNAs that change expression during the adipogenic differentiation of porcine bone marrow stem cells (BMSCs), with a focus on miR-29c.
  • Over-expressing miR-29c inhibits both the growth and fat cell formation of BMSCs by targeting IGF1 and affecting key signaling pathways like MAPK and PI3K-AKT-mTOR.
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Pigs are widely used as animal models in various studies related to humans. The interaction between the gut microbiota and the host has significant effects on the host's health and disease status. However, although there have been many studies investigating the pig gut microbiota, the findings have been inconsistent due to variations in rearing conditions.

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The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously demonstrated. Acetate is the predominant short-chain fatty acids synthesized by gut microbiota through the fermentation of dietary fiber; however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during the rapid growth stage remains to be further elucidated.

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Unlike other poultry, parent pigeons produce "pigeon milk" in their crops to nurture their squabs, which is mainly controlled by prolactin (PRL). Exception for PRL, the pituitary gland may also release various other peptide and protein hormones. However, whether these hormones change during pigeon crop lactation and their potential physiological functions remain unclear.

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In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting.

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Cebpa is a master transcription factor gene for adipogenesis. However, the mechanisms of enhancer-promoter chromatin interactions controlling Cebpa transcriptional regulation during adipogenic differentiation remain largely unknown. To reveal how the three-dimensional structure of Cebpa changes during adipogenesis, we generated high-resolution chromatin interactions of Cebpa in 3T3-L1 preadipocytes and 3T3-L1 adipocytes using circularized chromosome conformation capture sequencing (4C-seq).

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Background: Allele-specific expression (ASE) refers to the preferential expression of one allele over the other and contributes to adaptive phenotypic plasticity. Here, we used a reciprocal cross-model between phenotypically divergent European Berkshire and Asian Tibetan pigs to characterize 2 ASE classes: imprinting (i.e.

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Using an adult female miniature pig model with diet-induced weight gain/weight loss, we investigated the regulatory mechanisms of three-dimensional (3D) genome architecture in adipose tissues (ATs) associated with obesity. We generated 249 high-resolution in situ Hi-C chromatin contact maps of subcutaneous AT and three visceral ATs, analyzing transcriptomic and chromatin architectural changes under different nutritional treatments. We find that chromatin architecture remodeling underpins transcriptomic divergence in ATs, potentially linked to metabolic risks in obesity development.

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Pigeons (Columba livia) are among a select few avian species that have developed a specialized reproductive mode wherein the parents produce a 'milk' in their crop to feed newborn squabs. Nonetheless, the transcriptomic dynamics and role in the rapid transition of core crop functions during 'lactation' remain largely unexplored. Here, we generated a de novo pigeon genome assembly to construct a high resolution spatio-temporal transcriptomic landscape of the crop epithelium across the entire breeding stage.

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Lacking PTRF (polymerase I and transcript release factor), an essential caveolae component, causes a secondary deficiency of caveolins resulting in muscular dystrophy. The transcriptome responses of different types of muscle fibers and mononuclear cells in skeletal muscle to muscular dystrophy caused by Ptrf deletion have not been explored. Here, we created muscular dystrophy mice by Ptrf knockout and applied single-nucleus RNA sequencing (snRNA-seq) to unveil the transcriptional changes of the skeletal muscle at single-nucleus resolution.

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Article Synopsis
  • The study focuses on TMEM8c (Myomaker), a protein important for skeletal muscle development, particularly in pigs.
  • Researchers found that miR-205 inhibits myoblast fusion by targeting Myomaker, complicating muscle growth and healing.
  • When analyzing muscle injury in pigs, they observed that Myomaker expression increased while miR-205 decreased, suggesting a critical role for Myomaker in muscle regeneration.
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  • The study investigates the 3D genome structures of human adipose tissues (ATs) compared to six other mammals, aiming to uncover unique aspects of human metabolic regulation.
  • It identifies both evolutionarily conserved and human-specific chromatin configurations, highlighting that human-specific promoter-enhancer interactions (PEIs) are more dynamic and less conserved than their counterparts.
  • The research finds that genes related to energy metabolism in humans are linked with unique chromatin organization, while conserved genes are more associated with general housekeeping functions, revealing significant differences in genomic regulation between humans and other mammals.
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Macrophages are the foremost controllers of innate and acquired immunity, playing important roles in tissue homeostasis, vasculogenesis, and congenital metabolism. In vitro macrophages are crucial models for understanding the regulatory mechanism of immune responses and the diagnosis or treatment of a variety of diseases. Pigs are the most important agricultural animals and valuable animal models for preclinical studies, but there is no unified method for porcine macrophage isolation and differentiation at present; no systematic study has compared porcine macrophages obtained by different methods.

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This study aims to compare the fecal microbiome-metabolome response to copper sulfate (CuSO) and copper glycinate (Cu-Gly) in pigs. Twelve Meishan gilts were allocated into the CuSO group and the Cu-Gly group (fed on a basal diet supplemented with 60 mg/kg copper from CuSO or Cu-Gly) paired in litter and body weight. After a two-week feeding trial, the Cu-Gly group had a higher copper digestibility, blood hemoglobin, and platelet volume and higher levels of plasma iron and insulin-like growth factor-1 than the CuSO group.

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Animal fat deposition has a significant impact on meat flavor and texture. However, the molecular mechanisms of fat deposition are not well understood. Lnc-AS is a naturally occurring transcript that is abundant in porcine adipose tissue.

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The breast muscle is essential for flight and determines the meat yield and quality of the meat type in pigeons. At present, studies about long non-coding RNA (lncRNA) expression profiles in skeletal muscles across the postnatal development of pigeons have not been reported. Here, we used transcriptome sequencing to examine the White-King pigeon breast muscle at four different ages (1 day, 14 days, 28 days, and 2 years old).

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Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important regulatory role in development and function of innate immune cells and T cells, but their role in B cell biology is still controversial.

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