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Cell This Week Includes Four Malignant Cellular States of Glioblastoma, More

Malignant cells in glioblastoma largely fall into four main cellular states, according to a new study appearing in Cell. A Harvard Medical School-led team conducted single-cell RNA-sequencing of 20 adult and eight pediatric glioblastoma cases for a total 24,131 cells, single-cell RNA-sequencing and lineage tracing of glioblastoma models, and bulk analysis of 401 samples from The Cancer Genome Atlas to pull together an integrative model of glioblastoma. They found that malignant cells in glioblastoma largely resemble one of four cellular states — neural-progenitor-like, oligodendrocyte-progenitor-like, astrocyte-like, and mesenchymal-like states — though the proportion present in each tumor varies. Additionally, they report that genetic drivers of glioblastoma appear to influence frequency of those states.

A Stanford University-led team describe in a paper in Cell a new method for predicting long-term outcomes among cancer patients. Dubbed Continuous Individualized Risk Index (CIRI), their approach combines pre-disease, interim, and end-of-treatment risk factors, such as circulating tumor DNA levels and imaging data, collected over time to yield a personalized prediction of clinical outcomes. When the researchers applied their approach to a cohort of diffuse large B cell lymphoma patients, they report that it improved upon conventional risk prediction models. Further, in chronic lymphocytic leukemia and breast adenocarcinoma patients, they note that this approach could also be used to develop predictive markers for therapy selection.

Finally, Dutch researchers report that they used a genome-wide CRISPR/Cas9 screen to uncover parts of the tumor necrosis factor (TNF) pathway that, when targeted, could sensitize tumors to a T cell attack. When the top hit, TRAF2, is depleted, the researchers found tumors had increased sensitivity to T cell killing, lowering the TNF cytotoxicity threshold. Further, targeting both TRAF2 and cIAP1, which it interacts with, increases the effectiveness of immune checkpoint blockade therapy. This suggested to them that lowering the TNF cytotoxicity threshold could boost tumors' response to immunotherapies.

The Scan

Machine Learning Helps ID Molecular Mechanisms of Pancreatic Islet Beta Cell Subtypes in Type 2 Diabetes

The approach helps overcome limitations of previous studies that had investigated the molecular mechanisms of pancreatic islet beta cells, the authors write in their Nature Genetics paper.

Culture-Based Methods, Shotgun Sequencing Reveal Transmission of Bifidobacterium Strains From Mothers to Infants

In a Nature Communications study, culture-based approaches along with shotgun sequencing give a better picture of the microbial strains transmitted from mothers to infants.

Microbial Communities Can Help Trees Adapt to Changing Climates

Tree seedlings that were inoculated with microbes from dry, warm, or cold sites could better survive drought, heat, and cold stress, according to a study in Science.

A Combination of Genetics and Environment Causes Cleft Lip

In a study published in Nature Communications, researchers investigate what combination of genetic and environmental factors come into play to cause cleft lip/palate.