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Cell Papers on Glioma Progression, Genome-Wide Perturb-Seq, Multiple Sclerosis

A team from the Jackson Laboratory for Genomic Medicine and other international centers share findings from an analysis of tumor and microenvironment features linked to glioma progression. Using a combination of RNA sequencing, DNA sequencing, and other approaches, the researchers profiled samples collected at different time points in 304 adult glioma cases involving isocitrate dehydrogenase (IDH) enzyme-mutant or IDH-wild type tumors. Among other findings, they saw distinct features in recurring tumors with or without IDH mutations, including enhanced invasiveness and an uptick in neuronal signaling expression in neoplastic cells from the IDH-wild type tumors that returned. Even so, the authors note, both IDH-mutant and -wild type tumors tended to show a rise in CDKN2A gene deletions and hypermutation in the proliferating cells that appeared at recurrence. "Collectively," they write, "these recurrence-associated phenotypes represent potential targets to alter disease progression."

Investigators at the University of California, San Francisco, the Massachusetts Institute of Technology, and elsewhere demonstrate the possibility of using Perturb-seq phenotypic screening to explore genotype-phenotype relationships. The approach relied on CRISPR gene editing-based interference for systematically targeting expressed genes in large sets of individual cells assessed by single-cell RNA sequencing, the team notes. When they used this approach to screen millions of individual cells, for example, the authors were able to predict gene roles and regulatory networks based on transcriptional features. "In addition to assigning gene function, single-cell transcriptional phenotypes allow for in-depth dissection of complex cellular phenomena — from RNA processing to differentiation," they write, noting that a genotype-phenotype map generated with their own analyses "reveals a multidimensional portrait of gene and cellular function."

A team from Tianjin Medical University and other centers in China outlines bone marrow-related contributions to the progression of multiple sclerosis (MS), a nervous system condition marked by autoimmune features involving the immune system's T cells. With single-cell RNA sequencing, flow cytometry, and other approaches, the researchers compared HSPC and differentiated cell lineage patterns in bone marrow samples from individuals with or without MS, uncovering a bias toward the myeloid immune cell lineage and T cell clonal expansion in the MS patients — results they explored and spelled out further in a mouse model. "Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders," the authors write.

The Scan

Pig Organ Transplants Considered

The Wall Street Journal reports that the US Food and Drug Administration may soon allow clinical trials that involve transplanting pig organs into humans.

'Poo-Bank' Proposal

Harvard Medical School researchers suggest people should bank stool samples when they are young to transplant when they later develop age-related diseases.

Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.