In this week's Science, a team of British researchers present a study in which they use single-cell mRNA sequencing of human renal cells to characterize the origin of malignant cells and tumor tissue diversity. Using a collection of 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys, as well as a reference map of normal mature and fetal kidney cells, the researchers show that childhood Wilms tumor cells match specific fetal cell types, suggesting that the cancer originates with aberrant fetal cells. In adult renal cell carcinoma, they find a canonical cancer transcriptome that matches a little-known subtype of proximal convoluted tubular cell. The study, the researchers conclude, "provides a scalable experimental strategy for determining the identity of human cancer cells." GenomeWeb has more on this, here.
Also in Science, Harvard's George Church and colleagues present a new CRISPR-based method for in vivo cell barcoding and lineage tracing in the whole mouse. The approach involves multiple homing guide RNAs — placed throughout the genomes of mouse embryonic stem cells — that each generate hundreds of mutant alleles and combine for an exponential diversity of barcodes. Activation uponconception and continued mutagenesis through gestation result in developmentally barcoded mice wherein information is recorded in lineage-specific mutations, the authors say. They use the recordings to reliably reconstruct the earliest lineages to organ development, specifically studying axis development in the brain. "Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system," the researchers write.