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Cell Papers on Brain Metastases, COVID-19 Blood Atlas, Heart Disease Transcription Factor Interactomes

Investigators at the University of California, San Francisco, Rockefeller University, and elsewhere present findings from a brain metastasis profiling study. The team performed 10x Genomics single-cell RNA sequencing on more than 100,000 malignant and normal cells isolated from 15 metastatic brain tumors in individuals with up to eight primary cancer types. Together with mass cytometry, mouse modeling, and in silico analysis data, the single-cell transcriptomes offered a look at metastatic tumor interactions with immune cells and other tumor microenvironment features, while highlighting distinct metastatic clusters. "Collectively, these programs delineate two functional [brain metastasis] archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions," the authors report. "Our resource provides a foundation to understand the molecular basis of [brain metastasis] in patients with tumor cell-intrinsic and host environmental traits."

Members of the "COVID-19 Multi-omics Blood Atlas" (COMBAT) Consortium outline efforts to uncover blood features associated with human host responses to SARS-CoV-2 infections, including immune signatures linked to severe disease, COVID-19-specific features, and immune signals that resemble those in individuals with other conditions such as influenza or sepsis. Using a combination of whole blood RNA-seq­, B-cell and T-cell receptor sequencing, CITE-seq, and other approaches, the team profiled immune features in relation to clinical characteristics in 116 hospitalized individuals with COVID-19, comparing the immune signatures with those linked to sepsis or severe flu infections. The authors note that ongoing AP-1/p38MAPK-related immune pathway activation appeared to be a COVID-19-specific response, for example. They suggest that their comprehensive profiling approach and resulting blood atlas "will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19."

Finally, a team led by investigators at the Gladstone Institutes and the University of California, San Francisco, describes transcription factor protein interactomes linked to congenital heart disease (CHD), focusing on the GATA4 and TBX5 transcription factors. Based on GATA4 and TBX5 interactions in human cardiac progenitor cells, together with protein-coding sequence data for thousands of parent-child trios, the researchers suggest that CHD-related de novo variants may be over-represented in the transcription factor interactomes considered. "We hypothesized that genetic determinants for CHD may lie in the protein interactomes of transcription factors whose mutations cause CHDs," the researchers explain, noting that the study's "integrative proteomic and genetic approach provides a framework for prioritizing and interrogating genetic variants in heart disease."

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