The butyrophilin 1a1 knock-out mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA754402 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15444240_1.fastq.gz | Fastqsanger.gz | |||
| SRR15444240_2.fastq.gz | Fastqsanger.gz | |||
| SRR15444241_1.fastq.gz | Fastqsanger.gz | |||
| SRR15444241_2.fastq.gz | Fastqsanger.gz | |||
| SRR15444242_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Purpose: To assess global changes to the levels of mRNA and protein in butyrophilin-null mice (Btn1a1-/-), which were previously shown to be defective in regulated milk-lipid secretion in the lactating mammary gland. Methods: mRNA profiles of wild-type (WT) and Btn1a1-/-mice were generated by mRNA/cDNA library preparation (Illumina), qPCR quantitation, cluster generation and pair-end deep sequencing (Illumina HiSeq 4000 sequencer) using an Illumina HiSeq SBS kit. Changes in mRNA levels (null/WT ≥ ± 2-fold; adjusted p ≤ 0.05) were assesed by GSEA and IPA analysis and compared with a proteomic analysis of the same sample set.. Results: Samples had 95-167 million pass filter reads (92% above Q30). Mapping of all samples was > 97% (mm10 reference genome). Significant changes in mRNA amounts accounted for 1.4% of 11,834 transcipts (113 up and 53 down regulated). Only 10 mRNA/protein pairs were significantly upregulated and one (Btn1a1) downregulated. Pathways and networks associated with inflammation, apoptosis and the cell cycle were upregulated and lipid synthesis and metabolism were downregulated. Biochemical and histochemical analysis confirmed that lactation is maintained in null animals, in the face of significant apoptosis, by the continual regeneration of secretory epithelial cells. Cell death proceeded through several pathways including activation of caspases 8 and 3 and not by the lysosomal lysis pathway predominant in WT cells Conclusions: Ablation of Btn1a1 has multiple effects on milk-secreting mammary cells, including disruption of lipid secretion, increased cell damage and death. Lactation is maintained by continuous regeneration of the epithelium. Expression of functional Btn1a1 is essential for the maintainance of terminally differentiated mammary cells and optimal milk production throughout lactation.
2021-09-20 | GSE182075 | GEO
Project description:Butyrophilin 1A1 (BTN1A1) was first identified as a major integral protein of both the apical surface of mammary epithelial cells during lactation and the surface membrane surrounding lipid droplets in milk. Current evidence supports a role for BTN1A1 in the secretion of milk lipids as a membrane receptor, which forms a secretion complex with the redox enzyme, xanthine oxidoreductase (XDH). Capping of cytoplasmic lipid droplets with BTN1A1 and XDH serves to envelop the droplets with cellular membranes at the cell apex as an initial step in their subsequent release from the cell. The first evidence that BTN1A1 functions in this process was the generation of Btn1a1-/- mice, in which lipid secretion was disrupted and large unstable droplets were released into alveolar spaces with fragmented surface membranes. We have revisited this mutant mouse line using RNAseq and proteomic analysis to fully assess the consequences of ablating the Btn1a1 gene on the expression of other genes and proteins. Disruption of Btn1a1 expression led to a large build-up of Xdh (6-fold over wild-type levels) in the cytoplasm, induction of acute phase response genes and Lif-activation of STAT3 phosphorylation. At peak lactation, approx. 10% of the cells were dying, as assessed by TUNEL-analysis of nuclear DNA. Cell death appeared to proceed through expression of caspase 8 and activated caspase 3 and not via lysosomal lysis, which is the principal route for elimination of cells during mammary involution in wild-type mice. Other potential death pathways include autophagy and Slc5a8-mediated inactivation of survivin (Birc5). Milk secretion was prolonged by renewal of the secretory epithelium, as evidenced by the expression of cyclins, Fos/Jun and upregulation of Ki67 in approx. 10% of secretory cell nuclei. Thus a 21-day lactation cycle can be maintained, despite significant cell death by compensatory cell division, provided a milking stimulus is maintained. These data highlight the importance of BTN1A1 expression for the maintenance of terminally differentiated mammary epithelial cells and optimal milk production throughout lactation. From a practical standpoint, the complimentary RNAseq and proteomics data should provide a useful reference database for gene and protein expression in C57/Bl6 mice at peak lactation.
2021-09-20 | PXD021249 | Pride
Project description:Butyrophilin 1A1 (BTN1A1) is implicated in the secretion of lipid droplets from mammary epithelial cells as a membrane receptor, which forms a secretion complex with the redox enzyme, xanthine oxidoreductase (XDH). The first evidence that BTN1A1 functions in this process was the generation of Btn1a1 -/- mouse lines, in which lipid secretion was disrupted and large unstable droplets were released into alveolar spaces with fragmented surface membranes. We have revisited one of these mutant mouse lines using RNAseq and proteomic analysis to assess the consequences of ablating the Btn1a1 gene on the expression of other genes and proteins. Disruption of intact Btn1a1 protein expression led to a large build-up of Xdh in the cytoplasm, induction of acute phase response genes and Lif-activation of Stat3 phosphorylation. At peak lactation, approx. 10% of the cells were dying, as assessed by TUNEL-analysis of nuclear DNA. Possible cell death pathways included expression of caspase 8 and activated caspase 3, autophagy, Slc5a8-mediated inactivation of survivin (Birc5), and pStat3-mediated lysosomal lysis, the latter of which is the principal death route in involuting wild type cells. Milk secretion was prolonged by renewal of the secretory epithelium, as evidenced by the upregulation of Ki67 in approx. 10% of cell nuclei and expression of cyclins and Fos/Jun. These data highlight the plasticity of the mammary epithelium and the importance of functional BTN1A1 expression for maintenance of terminally differentiated secretory cells and optimal milk production throughout lactation.
| S-EPMC8664049 | biostudies-literature
Project description:Bacillus subtilis strain:1A1 Genome sequencing and assembly
| PRJNA670247 | ENA
Project description:Draft genome sequence of Bacillus thermoamylovorans 1A1
| PRJEB6526 | ENA
Project description:Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.
2023-04-01 | GSE137832 | GEO
Project description:Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.
2021-06-04 | GSE176118 | GEO
Project description:In comparison with cow milk, goat (Capra hircus) milk contains much higher levels of unsaturated fatty acids, as well as higher levels of total fat, proteins, carbohydrates, calcium, and vitamins.The main objective of the present study was to better define the relationship of known miRNAs regulating milk fat metabolism. Our main purpose is to search for some known miRNAs regulating milk fat metabolism, to this end, we screened potential miRNAs with differential expression between peak-lactation and non-lactation.
2016-06-25 | GSE83706 | GEO
Project description:Dynamic transcriptome profiles in yak mammary gland were evaluated by sampling mammary tissue at -30, -15, 1, 15, 30, 60, 120, 180 and 240 d relative to parturition and using a bovine commercial microarray platform. Several bioinformatics tools were used to analyze the data, both as expression relative to -30 d and as expression relative to the previous time point. There were >6,000 differentially expressed transcript (DEG; FDR＜0.05; P＜0.05) throughout lactation with larger DEG observed at the onset (1 vs. -15d) and at the end of lactation (240 vs. 180d). Bioinformatics analysis allowed to identify lactation-related genes on yak chromosomes which laid the foundation for determination of QTL location. Among most-impacted bovine chromosomes (BTA), BTA6, BTA9 and BTA28 were induced while BTA3, BTA4 and BTA14 were inhibited throughout lactation. Functional analysis underlined an overall induction of lipid metabolism, suggesting increases in triglycerides synthesis likely regulated by PPAR signaling. Data suggested induction of amino acid metabolism while increasing secretion or protein, but decreasing proteasome, indicating a major role of amino acid handling and reduced protein degradation in the synthesis and secretion of milk proteins. Glycan biosynthesis, both for N-glycan and O-glycan, was induced suggesting increased glycan content in milk. Cell cycle and immune response, especially antigen processing and presentation, were strongly inhibited during lactation suggesting morphological changes were minimized while the mammary gland prevents immune hyper responses during lactation. Transcripts associated with response to radiation and low oxygen were enriched in the down-regulated DEG affected by stage of lactation. Except for the latter, functions affected by the transcriptomic adaptation to lactation in mammary tissue of yak were very similar to the ones observed in dairy cows.
2022-04-28 | GSE201438 | GEO
Project description:Transcriptional regulation by Aire in medullary thymic epithelial cells revisited
| PRJNA649427 | ENA