Project description:RNA Sequencing was performed on RNA extracted from human bone marrow B cells from NSG humanized mice that had been transplanted with human hematopoietic stem cells and then injected or not with the ATM inhibitor KU55933.
Project description:Comparative expression between hT-ALL cells isolated from NSG mouse thorax vertebrae (adipocyte poor) bone marrow and from tail vetretbrae (adipocyte rich) bone marrow We used microarrays to understand the global program of gene expression underlying hT-ALL behaviour in two different bone marrow sites
Project description:To uncover the identity of the HGF-independent stromal-mediated resistance mechanism(s), we performed transcriptomic analyses of treatment-naïve and alectinib-treated H3122 xenograft tumors from NSG and humanized HGF-NSG (hHGF-NSG) mice. Xenograft tumors of H3122 cell model were used to perform bulk-RNA sequencing. Reads were mapped to both human and murine genomes, enabling simultaneous assessment of the tumor and stromal compartments. Our transcriptional analyses revealed the emergence of the HGF-dependent differences only after six weeks of alectinib treatment. Pathway enrichment analyses revealed marked changes in multiple pathways associated with extracellular matrix (ECM). Altogether, the transcriptomic analysis supported the potential involvement of tumor cell-ECM interactions in HGF-independent mediation of stromal-mediated resistance to alectinib.
Project description:To determine what signalling pathways are affected by LILRB1 in MM cells, ARP-1 MM cell lines were transfected with lentivirus to knockdown LILRB1, injected to nsg mice, sorted from the bone marrow of NSG mice and sent for RNA-seq. Total RNAs of 2 x 10^6 CTR-KD ARP-1 cells or LILRB1-KD ARP-1 cells were extracted by RNeasy Mini Kit (Qiagen). 5-10 µg RNA samples were sent to Cancer Genomics Center at The University of Texas (Houston, TX) for RNA-seq followed by data analysis. We use the RNA-seq data to determine differential expression of genes in CTR-KD ARP-1 cells and LILRB1-KD ARP-1 cells.
Project description:SARS-CoV2 mRNA vaccine-induced side effects have been extensively reported in the clinical field. However, the potential toxicity of mRNA vaccines has not been fully identified. We aimed to clarify mRNA vaccine-induced bone marrow toxicity. Six-week-old CrlOri:CD1(ICR) female mice were used. A SARS-CoV2 S protein coding nucleoside-modified mRNA vaccine candidate or D-PBS (Negative control) was intramuscularly injected at left side femoral muscle twice at 2-week intervals (100 ug/head). Mice were sacrificed at 2 days post-secondary injection, and the bulk RNA sequencing for bone marrow of left side femur was performed. Notably, the mRNA vaccine induced significant decrease of erythroid cells in bone marrow. The bone marrow suppression was mediated by the complete mRNA vaccine, but not by mRNA only or LNP only. The RNA sequencing revealed that interferon-stimulated genes (ISGs), cell death-related genes and proteolysis-related genes were significantly upregulated, while erythrocyte development-related genes, hematopoietic cell differentiation-related genes and cytoskeleton-related genes were downregulated, in the bone marrow tissue of mRNA vaccine-injected mice compared to that of only LNP-injected mice. These findings indicate that the mRNA template is mainly involved in the mRNA vaccine-induced bone marrow suppression. We confirmed that the mRNA vaccine can cause pathological changes in bone marrow tissue. Although the underlying mechanism needs to be clarified, our findings suggest that mRNA vaccine-induced bone marrow suppression should be cautiously considered in the pre-clinical developmental process.
Project description:SARS-CoV2 mRNA vaccine-induced side effects have been extensively reported in the clinical field. However, the potential toxicity of mRNA vaccines has not been fully identified. We aimed to clarify mRNA vaccine-induced bone marrow toxicity. Six-week-old CrlOri:CD1(ICR) female mice were used. A SARS-CoV2 S protein coding nucleoside-modified mRNA vaccine candidate or D-PBS (Negative control) was intramuscularly injected at left side femoral muscle twice at 2-week intervals (100 ug/head). Mice were sacrificed at 2 days post-secondary injection, and the bulk RNA sequencing for bone marrow of left side femur was performed. Notably, the mRNA vaccine induced significant decrease of erythroid cells in bone marrow. The bone marrow suppression was mediated by the complete mRNA vaccine, but not by mRNA alone or LNP alone. The RNA sequencing revealed that interferon-stimulated genes (ISGs), cell death-related genes and proteolysis-related genes were significantly upregulated, while erythrocyte development-related genes, hematopoietic cell differentiation-related genes and cytoskeleton-related genes were downregulated, in the bone marrow tissue of mRNA vaccine-injected mice compared to that of D-PBS-injected mice. These findings indicate that the mRNA template is involved in the mRNA vaccine-induced bone marrow suppression. We confirmed that the mRNA vaccine can cause pathological changes in bone marrow tissue. Although the underlying mechanism needs to be clarified, our findings suggest that mRNA vaccine-induced bone marrow suppression should be cautiously considered in the pre-clinical developmental process.