Study: Sensitive spatial genome wide expression profiling at cellular resolution 0 cells

"Sensitive spatial genome wide expression profiling at cellular resolution."

Stickels, Murray et al., Biorxiv 2020.

Abstract: The precise spatial localization of molecular signals within tissues richly informs the mechanisms of tissue formation and function. Previously, we developed Slide-seq, a technology which enables transcriptome-wide measurements with 10-micron spatial resolution. Here, we report new modifications to Slide-seq library generation, bead synthesis, and array indexing that markedly improve the mRNA capture sensitivity of the technology, approaching the efficiency of droplet-based single-cell RNAseq techniques. We demonstrate how this modified protocol, which we have termed Slide-seqV2, can be used effectively in biological contexts where high detection sensitivity is important. First, we deploy Slide-seqV2 to identify new dendritically localized mRNAs in the mouse hippocampus. Second, we integrate the spatial information of Slide-seq data with single-cell trajectory analysis tools to characterize the spatiotemporal development of the mouse neocortex. The combination of near-cellular resolution and high transcript detection will enable broad utility of Slide-seq across many experimental contexts.

Data Download: Data supporting the findings above is available for download through this study, produced in the labs of Fei Chen and Evan Macosko. For each Slide-seqV2 puck used, we have provided a raw counts digital gene expression (DGE) matrix (.txt.gz) and a bead barcode locations file (.csv). The pucks are used throughout figures and analyses as follows. The protocol used for generating the data is noted as Slide-seq or the new Slide-seqV2 protocol:

Figure 1A: Left, Puck_190921_21 (mouse hippocampus, Slide-seqV2), right, Puck_200115_08 (mouse hippocampus, Slide-seqV2)

Figure 1B: Puck_190926_03 (mouse embryo Slide-seqV2), Puck 191007_07 (mouse embryo Slide-seq)

Figure 1C/D: Puck_190921_21(mouse hippocampus, Slide-seqV2)

Figure 2A-G: Puck_191204_01 (mouse hippocampus, Slide-seqV2)

Figure 3: Puck_190921_19 (mouse E15 brain Slide-seqV2)

Figure S3: Puck_200115_08 (mouse hippocampus, Slide-seqV2), visium data is coronal section from 10x website

Figure S4: Puck_191204_01 (mouse hippocampus, Slide-seqV2)

Figure S6: Puck_190921_19 (mouse E15 brain, Slide-seqV2)

Supp. Table 7: Puck_190926_01, Puck_190926_02, Puck_190926_03, Puck_190926_06 (Mouse E12.5 embryo sections, Slide-seqV2)