Project description:The RNA genome of the SARS-CoV-2 virus encodes for four structural proteins, 16 non-structural proteins and nine putative accessory factors. A high throughput analysis of interactions between human and SARS-CoV-2 proteins identified multiple interactions of the structural Nucleocapsid (N) protein with RNA processing factors. The N-protein, which is responsible for packaging of the viral genomic RNA was found to interact with two RNA helicases, UPF1 and MOV10 that are involved in nonsense-mediated mRNA decay (NMD). NMD is a translation-coupled mechanism that targets mRNAs harboring a premature stop codon (PTC) for degradation, thereby serving as a quality control and gene regulatory pathway ensuring transcriptome integrity. Here, we wanted to explore the impact of transiently expressed N protein on the transcriptome of human embryonic kidney cell line HEK293 by RNA-Sequencing. To this end, the SARS-CoV2-N protein was transiently expressed from a pcDNA3.1-HA-N plasmid for 48 hours and the corresponding empty vector was used as a control.
Project description:In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
Project description:Experiment was designed to study the effect of Hippo pathway on osimertinib resistance in non-small cell lung cancer cell lines. The specific comparisons investigated were: PC-9: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE, EV DMSO treated vs EV osimertinib treated HCC827: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE,EV DMSO treated vs EV osimertinib treated HCC4006: NTC vs NF2 KO, EV vs YAP1 OE, EV vs WWTR1 OE, EV DMSO treated vs EV osimertinib treated
Project description:Defective endometrial stromal fibroblasts (EMSF) contribute to uterine factor infertility, endometriosis and endometrial cancer. Induced pluripotent stem cells (iPSC) derived from skin or bone marrow biopsies provide a patient-specific source that can be differentiated to various cells types. Replacement of abnormal EMSF is a potential novel therapeutic approach for endometrial disease; however, the methodology or mechanism for differentiating iPSC to EMSF is unknown. The uterus differentiates from the intermediate mesoderm (IM) to form coelomic epithelium (CE) followed by the Müllerian duct (MD). Here, we successfully directed the differentiation of human iPSC (hiPSC) through IM, CE and MD to EMSF under molecularly defined embryoid body culture conditions using specific hormonal treatments. Activation of CTNNB1 was essential for expression of progesterone receptor that mediated the final differentiation step of EMSF before implantation. These hiPSC-derived tissues illustrated the potential for iPSC-based endometrial regeneration for future cell-based treatments.
Project description:Developmental experiences play critical roles in shaping adult physiology and behavior. We and others previously showed that adult C. elegans which transiently experienced dauer arrest during development (PD: post-dauer) exhibit distinct gene expression profiles as compared to control adults which bypassed the dauer stage. In particular, the expression patterns of subsets of chemoreceptor genes are markedly altered in PD adults. Whether altered chemoreceptor levels drive plasticity in chemosensory behaviors in PD adults is unknown. Via transcriptional profiling of sorted populations of AWA neurons from control and PD adults, we further show that the expression of a subset of chemoreceptor genes in AWA are differentially regulated in PD animals. Our results suggest that developmental experiences may be encoded at the level of olfactory receptor regulation, and provide an elegant mechanism by which C. elegans is able to precisely modulate its behavioral preferences as a function of its current and past experiences.
Project description:Stress-related illness represents a major burden on health and society. Understanding the molecular mechanisms underlying stress responses is an important step to understand these diseases, and design treatments. Sexual dimorphism in stress responses have been extensively reported, with depression and most anxiety disorders being more prevalent in women. Corticotrophs of the anterior pituitary play a central role in the generation of hormonal stress responses, by secreting the stress hormone ACTH in response to stressful stimuli. However, their role in contributing to sexually dimorphic responses of the HPA axis is very poorly understood. We performed bulk RNA-sequencing of FACS-sorted corticotrophs from male and female POMC-GFP mice to determine the molecular determinants of sexual dimorphic traits in the activity of these cells, revealing extensive differential gene expression at the transcriptional level. This includes more than 71 mRNAs encoding ion channel subunits, which could be involved in the generation of the sexual dimorphism in their electrical activity.
Project description:Stress-related illness represents a major burden on health and society. Understanding the molecular mechanisms underlying stress responses is an important step to understanding these diseases and designing treatments. Corticotrophs of the anterior pituitary play a central role in the generation of hormonal stress responses, by secreting the stress hormone ACTH in response to stressful stimuli. However, it is poorly understood how they change in response to chronic stress, and whether they return to their original state after the stress has ended. We performed bulk RNA-sequencing of FACS-sorted corticotrophs from male POMC-GFP mice before or after exposure to chronic stress, and after 4 or 12 weeks of recovery, to determine the effect of chronic stress (and of recovery) on corticotrophs transcriptome. This revealed extensive differential gene expression, especially during the recovery period. N.B. Some of the control samples in this dataset (CM1, 2, and 3) are shared with the related experiment, E-MTAB-12885.
Project description:Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with Neisseria meningitidis or its ligand MafA .
Project description:Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with Borrelia burgdorferi or its ligand Erp23.
Project description:Using RNA sequencing to map differentially expressed genes in human brain microvascular endothelial cells challenged with DIII domain of protein E of WNV and DIII domain of protein E of TBEV.