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Science Papers Present New Single-Cell Spatial Transcriptomics Method, More

A new method for single-cell spatial transcriptomics that retains its high resolution while capturing spatial information at larger scales is described in this week's Science. Developed by a University of Washington-led team, the method — called sci-Space — is based on a previously developed approach — dubbed sci-Plex — for labeling nuclei using unmodified DNA oligos before single-cell RNA sequencing with combinatorial indexing. Aiming to use sci-Plex to capture spatial information, the researchers spatially arrayed unique combinations of labeling oligos and then transferred them to nuclei within a tissue slice by diffusion. The oligos, recovered in association with sci-RNA-seq profiles, capture each cell's approximate tissue coordinates upon sequencing. The team demonstrates sci-Space in developing mouse embryos, capturing approximate spatial coordinates and whole transcriptomes of about 120,000 nuclei. They also identified thousands of genes exhibiting anatomically patterned expression, leveraged spatial information to annotate cellular subtypes, showed that cell types vary substantially in their extent of spatial patterning, and revealed correlations between pseudotime and the migratory patterns of differentiating neurons. They write that sci-Space may aid in the construction of spatially resolved single-cell atlases of mammalian development.

The molecular mechanism underlying the DNA methylation reprogramming of the male germline in plants is described in Science this week. In plants, DNA methylation reprogramming occurs during gametogenesis, when global methylation levels shift, and thousands of loci are actively demethylated in gamete companion cells. In Arabidopsis thaliana, germline-specific methylation is catalyzed by the small RNA-directed DNA methylation pathway, which generally methylates transposable elements, but how genes specifically in the male germline are targeted and specifically selected for methylation is unknown. In their study, John Innes Centre scientists show that genic methylation in the male Arabidopsis germline is established by 24 nucleotide-long siRNAs transcribed from hypermethylated transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells — called tapetum — through activity of a chromatin remodeler absent in other anther cells. These tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm, as well as silence germline transposons to safeguard genome integrity, the investigators write.