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Cell Studies on Tumor Evolution in Mouse Model of Lung Cancer, Stereo-seq, Bacteriophage Responses

Using a genetically engineered "KP-Tracer" chimeric mouse model of lung adenocarcinoma, lineage tracing analyses, and single-cell RNA sequencing, a team from the University of California at San Francisco, the Massachusetts Institute of Technology, and elsewhere tracked lung cancer tumor evolution. Along with shifting cellular plasticity and transcriptome patterns, for example, the investigators highlighted rare tumor subclone expansions, along with spatially defined subclones linked to metastasis. "By integrating lineage and transcriptome data, we uncovered changes in cancer cell plasticity and parallel evolutionary paths of tumor evolution in this model, which could be profoundly altered by perturbing additional tumor suppressor genes commonly mutated in human tumors," the authors write. "We have also identified the subclonal origins, spatial locations, and cellular states of metastatic progression."

Investigators at BGI-Shenzhen and other international centers map organogenesis over eight stages of mouse development with an in situ RNA capture and Stereo-seq, a DNA nanoball-based patterned array method designed for detecting spatial transcriptomic features. "We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis," they write, noting that the investigators delved into the MOSTA dataset to untangle developing dorsal midbrain features. "Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development."

A National Jewish Health Center- and University of Pittsburgh-led team looks at responses to two engineered, Mycobacterium abscessus-targeting bacteriophage in a 26-year-old with cystic fibrosis (CF) who received a lung transplant to treat advanced lung disease and a treatment-refractory M. abscessus infection. With M. abscessus sequencing and other molecular analyses, coupled with clinical data and metabolic assays, the researchers tracked host and microbe responses to the so-called mycobacteriophages given intravenously. "Together our results derived from objective orthogonal markers provide a road map for successful phage treatment in the context of advanced CF lung disease," the authors write. "Understanding the time span associated with initial response, radiologic improvement, and culture conversion following the start of treatment are essential for future therapeutic applications and clinical trial designs, as is the use of complementary culture-independent markers of M. abscessus lysis.