Project description:Exosomes are membranous extracellular vesicles 50–100 nm in size and are involved in cellular communication via the delivery of proteins, lipids, and RNAs. Emerging evidence shows that exosomes play a critical role in cancer. A recent study has revealed that maternal and umbilical cord serum-derived exosomes may enhance endothelial cell proliferation and migration. However, the role of exosomes isolated from the human umbilical cord in cancer development has not been investigated. To explore the potential differences in the composition and function of proteins from umbilical cord blood exosomes and maternal serum exosomes, we conducted a proteomic analysis of exosomes by mass spectrometry and bioinformatics analysis. We used the CCK-8 assay and flow cytometry to study the biological effects of umbilical serum exosomes on hepatoma cells. Our study shows that umbilical cord blood is enriched with proteins involved in ECM-receptor interactions, which may be closely related to cell metastasis and proliferation. Our findings indicate that exosomes derived from human umbilical serum can suppress the viability of hepatoma cells and may induce apoptosis of hepatoma cells. This evidence suggests that umbilical cord serum-derived exosomes may be potential leads for the development of biotherapy for liver cancer.
Project description:Preeclampsia (PE) is characterized by new-onset hypertension after 20 weeks of pregnancy and results in high maternal and fetal mortality worldwide. It has been reported that PE is associated with abnormalities in the umbilical cord and cord blood. However, previous studies were focused primarily on the transcriptomics level, while the underlying gene regulatory landscapes are still unclear. Thus, we performed the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) using the umbilical cord blood samples collected from a patient with superimposed PE and three healthy donors to uncover the chromatin accessibility changes attributed to PE. We have identified genes associated with immunomodulation and hypoxia response that have higher chromatin accessibility close to their transcription start sites. Motif analysis indicated that the GATA family transcription factor binding was enriched in PE and may play an essential regulatory role in the disease progression. Overall, our findings provide an overview of gene regulatory programs and the corresponding downstream pathways associated with PE that may influence the placenta function and fetal growth.
Project description:Introduction. Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers and offspring during the life course. While the severe early-onset PE (EOPE) phenotype originates from impaired placentation in early pregnancy, late-onset PE (LOPE) is in particular associated with pre-existing maternal cardiovascular- and metabolic risk factors. We hypothesize that PE is associated with altered epigenetic programming of placental and fetal tissues and that these epigenetic changes might elucidate the increased cardiovascular- and metabolic disease susceptibility in PE offspring. Methods. A nested case-control study was conducted in The Rotterdam Periconceptional Cohort comprising 13 EOPE, 16 LOPE, and three control groups of 36 uncomplicated pregnancies, 27 normotensive fetal growth restricted (FGR) and 20 normotensive preterm birth (PTB) complicated pregnancies. Placental tissue, newborn umbilical cord blood leucocytes (UC-WBC) and umbilical vein endothelial cells (HUVEC) were collected and DNA methylation of cytosine-guanine dinucleotides was measured by the Illumina HumanMethylation450K BeadChip. An epigenome-wide analysis was performed by using multiple linear regression models. Results. Epigenome-wide tissue-specific analysis between EOPE and PTB controls revealed 5001 mostly hypermethylated differentially methylated positions (DMPs) in UC-WBC and 869 mostly hypomethylated DMPs in placental tissue, situated in or close to genes associated with cardiovascular-metabolic developmental pathways. Discussion. This study shows differential methylation in UC-WBC and placental tissue in EOPE as compared to PTB, identifying DMPs that are associated with cardiovascular system pathways. Future studies should examine these loci and pathways in more detail to elucidate the associations between prenatal PE exposure and the cardiovascular disease risk in offspring.
Project description:Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis- related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.
Project description:Human reticulocytes were enriched from human umbilical blood, and cultured in vitro for the production of reticulocyte-derived exosomes (HuRex)to unveil their proteomic composition. As research on the molecular-cargo of exosomes is largely confounded by the lack of a “gold-standard” methodology, we applied several approaches for obtaining HuRex prior to MS. HuRex preparations were obtained from cultures in absence of serum (AS) from three donors and isolated by means of size-exclusion chromatography (SEC) (n=3) and ultracentrifugation (UC) (n=3). HuRex preparations in the presence of serum were obtained from three other donors and purified by SEC (n=3) and UC (n=1).
Project description:We used microarray technology to establish the differential RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients compared with normal controls.
Project description:Fiber diet plays a beneficial role in neurocognitive disorders, like dementia and Alzheimer’s Disease. However, insufficient fiber consumption in public increases the concern about public health, particularly about neurocognitive diseases. To survey the association between fiber dietary and neurocognitive performances, mice were subjected to normal-fiber diet or low-fiber diet during gestation, and the neurocognitive functions of the offspring were assessed. We found that maternal low-fiber diet impaired the cognitive functions, and the impairments can be reversed by butyrate, rather than propionate intake. Mechanism studies showed that HDAC4 might become the most potential mediator in butyrate-dependent neurocognitive improvement. Besides, using human maternal serum and paired umbilical cord blood samples, we demonstrated that the SCFA levels in offspring are positively correlated with levels in maternal serum. Those results provide a solid basis for not only maternal fiber diet regulates neurocognitive functions in offspring through altering SCFA levels, but clinical practice in SCFAs-dependent maternal intervention for offspring health.
Project description:Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. Recently, the FDA has approved blood-based biomarkers, GFAP and UCH-L1, to evaluate the need for CT scans, however, clinical translation is currently limited. Exosomes are small microcellular vesicles which are released from the cell in both normal and diseased states, as part of extracellular communication. The aim of this study was to isolate neuronal exosomes derived from the serum of patients with severe TBI and characterize the messenger RNA content of the exosomes released by the injured neurons in order to identify new potential blood-based biomarkers. RNA was isolated from neuronal exosomes and total transcriptomic sequencing was performed. RNA sequencing data from neuronal exosomes isolated from serum showed mRNA transcripts of several neuronal genes. Additionally, the RNA sequencing data revealed mRNA of several olfactory receptor genes, which were present at elevated concentrations in the neuronal exosomes. Further validation in serum samples of mild TBI patients revealed a similar upregulation of olfactory receptors. The data from these experiments suggests that damage to the neurons in the olfactory neuroepithelium and in the brain, following a TBI, may cause the release of mRNA from these receptors in the exosomes. Thus, olfactory receptors can be further investigated as potential biomarkers for TBI diagnosis.