"By using time-resolved analyses of scRNA-seq data, we determined the potential transitional trajectories of tumor cells and identified the metastasis-initiating subpopulations"
https://link.springer.com/article/10.1007/s11684-024-1081-7
Reading right now. The identification of cells that initiate #metastasis are of interest, although n=2 paired primary and #BoneMarrow samples may be a bit limited.
Neuroblastoma (NB) is one of the most common childhood malignancies. Sixty percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor outcomes. However, the molecular mechanisms triggering NB metastasis remain largely uncharacterized. In this study, we generated a transcriptomic atlas of 15 447 NB cells from eight NB samples, including paired samples of primary tumors and bone marrow metastases. We used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common ‘starter’ subpopulation that initiates tumor development and metastasis. The ‘starter’ population exhibited high expression levels of multiple cell cycle-related genes, indicating the important role of cell cycle upregulation in NB tumor progression. In addition, our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition (p-EMT) along the metastatic route from the primary site to the bone marrow. Our study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.
While looking for #GeneExpression in tissues, specifically for #pediatric samples, I came across the #developmental #GTEx page, "a new effort to study development-specific genetic effects on gene expression from donors at each of 4 developmental windows".
https://gtexportal.org/home/aboutdGTEx
Exciting and important: for example the first age group, i.e. 0-2 years, in which our #Neuroblastoma patients often are, is mostly hard to compare to adult references and healthy controls.
The Genotype-Tissue Expression (GTEx) project is an ongoing effort to build a comprehensive public resource to study tissue-specific gene expression and regulation. Samples were collected from 53 non-diseased tissue sites across nearly 1000 individuals, primarily for molecular assays including WGS, WES and RNA-seq. Remaining samples are stored in the GTEx Biobank. The GTEx Portal provides open access to data including gene expression, QTLs, and histology images.
The oncoprotein MYCN drives oncogenesis in neuroblastoma by activating the expression of genes involved in ribosome biogenesis and protein synthesis, while repressing neuronal differentiation genes, but the underlying mechanisms remain unknown. This study shows that MYCN cooperates with the histone methyltransferase G9a and the WDR5 adaptor to orchestrate global gene transcription.
"Using two separate disease models previously known to be responsive to HDAC inhibitors, we evaluated the physiological effects of volatile exposure. Diacetyl exposure halted proliferation of a #neuroblastoma cell line in culture. Exposure to #diacetyl vapors slowed progression of neurodegeneration in a #Drosophila model for Huntington’s disease. These changes strongly suggest that certain volatiles in the surroundings can have profound effects on #histone acetylation"
Volatile compounds from microbes and food alter epigenetic states by inhibiting histone deacetylases and alter gene expression, slow degeneration in Huntington’s model flies, and slow proliferation of a neuroblastoma cell line.
Yesterday, me and my colleague took the #NightTrain to #Vienna, to join the #SIOPEN #translational research meeting.
Little under 10 hours from Utrecht.
I had to present our latest work on
#neuroblastoma. Beers to celebrate this event. 🍻
Important work, the #ITCC #SIOPEN #BEACON #neuroblastoma #trial
https://ascopubs.org/doi/10.1200/JCO.23.00458
In this trial Moreno et al. assessed possible added effects of #antiangiogenic agent #bevacizumab to #temozolomide treatment plus or minus #irinotecan or #topotecan for children with relapsed and refractory neuroblastoma.
Perhaps some early effects, but after 5-6 years rather depressing survival graphs, if I'm very honest.
"Integrative analysis of #neuroblastoma by single-cell RNA sequencing identifies the #NECTIN2-#TIGIT axis as a target for #immunotherapy"
https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00436-1
Great new work from Judith Wienke et al. from the Molenaar lab in the #PrincessMaximaCenter in #Utrecht.
Great to see this out after seeing it in our group meetings several times. In vivo results sometimes are impressive, but very much in a subgroup it seems. Intriguiging, and curious what underlies this.
Recent research led by Indiana University School of Medicine in collaboration with the University of Chicago Medicine presents exciting future possibilities for the management of type 1 diabetes and the potential reduction of insulin dependency. The researchers’ findings, published in Cell Reports M
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