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Mapping Single-Cell Genomic, Transcriptomic Landscapes of Colorectal Cancer

Using a variety of sequencing techniques, scientists from Peking University have generated maps of the single-cell genomic and transcriptomic landscapes of primary and metastatic colorectal cancer (CRC). The work, which appears in this week's Genome Medicine, sheds new light on the molecular mechanisms underlying the disease. While technological advances have enabled studies into the cellular and molecular basis of CRC carcinogenesis and metastasis, intratumoral heterogeneities and relationships among different omics of the cancer have not been systematically investigated. To do so, the researchers performed whole genome sequencing, multi-region whole exome sequencing, simultaneous single-cell RNA-sequencing, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic CRC patients. The PPAR signaling pathway, they find, is prevalently and aberrantly activated in CRC tumors. Further, in patient-derived tumor organoids, blocking this pathway suppressed the growth and promoted the apoptosis of CRC, suggesting that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. The investigators also combined single-cell RNA-seq and single-cell point mutation identification by targeted cDNA Sanger sequencing to uncover phenotypic differences between cancer cells with and without critical point mutations in the same patient in vivo at single-cell resolution. The work, the study's authors write, offers "novel knowledge on metastatic mechanisms, as well as potential markers and therapeutic targets for CRC diagnosis and therapy."

The Scan

Open Pediatric Brain Tumor Atlas Team Introduces Genomic Data Collection, Analytical Tools

A study in Cell Genomics outlines open-source methods being used to analyze and translate whole-genome, exome, and RNA sequence data from the Pediatric Brain Tumor Atlas.

Neurological Outcomes Linked to Innate Immune Features After Cardiac Arrest

Researchers reporting in Med dig into immune features found a few hours after cardiac arrest that correspond with neurological outcomes.

Mouse Study Finds Circadian Rhythm-Related Gene Expression Changes Linked to Sleep Apnea

A paper in PLOS Biology reveals tissue-specific circadian rhythm and gene expression patterns in an intermittent hypoxia-based mouse model of obstructive sleep apnea.

Polygenic Risk Score to Predict Preeclampsia, Gestational Hypertension in Pregnant Women

Researchers in Nature Medicine provide new mechanistic insights into the development of hypertensive disorders of pregnancy, which may help develop therapeutics.