Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays

TLDR

Spatially resolved transcriptomics promise to study complex biological processes such as mammalian embryogenesis, yet current methods lack a balance between resolution, gene capture, and field of view, limiting systematic application to large, three‑dimensional embryos. The authors developed Stereo‑seq, a DNA nanoball‑patterned array combined with in‑situ RNA capture, to generate a high‑resolution spatiotemporal atlas of mouse organogenesis and to use it to dissect spatial cell heterogeneity and fate specification. Stereo‑seq was applied to produce MOSTA, a single‑cell resolution atlas that maps the kinetics and directionality of transcriptional changes throughout mouse organogenesis with high sensitivity. MOSTA reveals detailed spatial and temporal transcriptional dynamics, providing insights into cell heterogeneity, fate decisions in tissues such as the dorsal midbrain, and enabling deeper investigation of normal and abnormal mammalian development.

Abstract

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). 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. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.