Maternal DBP exposure promotes synaptic formation in offspring by activiting astrocytes via AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway
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ABSTRACT:
PROVIDER: PRJNA779982 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16930984_1.fastq.gz | Fastqsanger.gz | |||
| SRR16930984_2.fastq.gz | Fastqsanger.gz | |||
| SRR16930985_1.fastq.gz | Fastqsanger.gz | |||
| SRR16930985_2.fastq.gz | Fastqsanger.gz | |||
| SRR16930986_1.fastq.gz | Fastqsanger.gz |
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Project description:In summary, we revealed that maternal DBP exposure activated astrocytes through the AKT/NF-κB/IL-6/JAK2/STAT3 signaling pathway and up-regulated the expression of TSP1, which then affected the density and morphology of dendritic spines and synaptic formation of hippocampal neurons, ultimately leading to decreased autonomy and exploration behavior of offspring.
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Project description:TEL-JAK2 is a fusion oncogene resulting from a t(9;12) chromosomal translocation in T-ALL, translated as a constitutively activated TEL-JAK2 tyrosine kinase. Mice carrying a TEL-JAK2 transgene develop T-ALL. Gene deregulated in TEL-JAK2 T-ALL cells as compared to mouse thymocytes were identified Leukemic cells were collected from the thymus of terminally-ill TEL-JAK2 mice; thymocytes were collected from the thymus of 2 months-old mice. All mice on C57B/6 background. RNA was extracted from each sample and processed for hybridization to Affymetrix arrays.
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Project description:TEL-JAK2 is a fusion oncogene resulting from a t(9;12) chromosomal translocation in T-ALL, translated as a constitutively activated TEL-JAK2 tyrosine kinase. Mice carrying a TEL-JAK2 transgene develop T-ALL. Gene deregulated in TEL-JAK2 T-ALL cells as compared to mouse thymocytes were identified
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Project description:SPAG9-JAK2 is a novel fusion gene identified in a pediatric patient with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). In this study, we performed functional analysis of the SPAG9-JAK2 fusion to establish molecular targeted therapy. Ba/F3 cells expressing SPAG9-JAK2 generated by retroviral transduction (Ba/F3-SPAG9-JAK2), proliferated in the absence of IL-3, and exhibited constitutive phosphorylation of the tyrosine residues in the JAK2 kinase domain of the fusion protein and STAT3/STAT5. Mutation of tyrosine residues in the JAK2 kinase domain (SPAG9-JAK2 mut) abolished IL-3 independence, but had no influence on STAT3/STAT5 phosphorylation levels. Gene expression analysis revealed that Stat1 was significantly up-regulated in Ba/F3-SPAG9-JAK2 cells. STAT1 was also phosphorylated in Ba/F3-SPAG9-JAK2 but not SPAG9-JAK2 mut cells, suggesting that STAT1 is key for SPAG9-JAK2-mediated cell proliferation. Consistently, STAT1 induced expression of the anti-apoptotic proteins, BCL-2 and MCL-1, as did SPAG9-JAK2, but not SPAG9-JAK2 mut. Ruxolitinib abrogated Ba/F3-SPAG9-JAK2-mediated proliferation in vitro, but was insufficient in vivo. Venetoclax (a BCL-2 inhibitor) or AZD5991 (an MCL-1 inhibitor) enhanced the effects of ruxolitinib on Ba/F3-SPAG9-JAK2 in vitro. These findings suggest that activation of the JAK2-STAT1-BCL-2/MCL-1 axis contributes to SPAG9-JAK2-related aberrant growth promotion. BCL-2 or MCL-1 inhibition is a potential therapeutic option for B-ALL with SPAG9-JAK2 fusion.
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