Wollman Lab | Research

Technology: We focus on developing spatial transcriptomics methods that prioritize scalability, believing that unlocking the full potential of spatial biology requires increasing mapping capacity by several orders of magnitude. Our goal is to enable whole-organ comparative studies across genetic backgrounds to better understand the relationship between organ structure (anatomy) and function (physiology). Recently, we introduced ATLAS (Atlas-scale Transcriptome Localization using Aggregate Signatures), which uses just 18 aggregate transcriptional signatures—dimensionally reduced approximations of cellular transcriptional states—to impute whole transcriptomes with accuracy comparable to imputations based on more than 1,000 genes. This use of aggregate signatures is fundamental to scaling atlases to tens of millions of cells.

Using ATLAS we mapped the mouse brains of 15 animals with over 400 full coronal sectios infering cell types and imputing trascriptomes of over 40,000,000 cell.

With this many cells, we can reconstruct cell type specific spatial distribution of hundreds of cell types across different genetic backgrounds

Theory: How do you build an organ with Lego-like bricks (cells) that differ from one another? How different are they—due to gene expression "noise" or functional heterogeneity? Is tissue architecture, the spatial arrangement of different cell types, inherently "noisy," and does this variability affect tissue function? What are the most informative ways to present organ atlases, and how does this change our understanding of organ organization? We tackle these questions using information theory and mathematical modeling to decode the relationships between cellular diversity, spatial organization, and organ functionality.

𝑆 𝑅 𝐼 (𝐺 𝑖, 𝐺 𝑗, 𝐶 𝑎 2 +) = 𝐼 (𝐺 𝑖, 𝐺 𝑗, 𝐶 𝑎 2 +) - 𝐼 (𝐺 𝑖, 𝐶 𝑎 2 +) - 𝐼 (𝐺 𝑗, 𝐶 𝑎 2 +)

Aplications: We work with a range of collaborators to leverage our mapping toolbox to understand mouse models of neurodevelopment, neurodegenerations, vaccination and cell-cell interactions in lymph nodes during vaccination, and more.