Pulmonary fibrosis (PF) is a heterogeneous clinical syndrome representing the end-stage of chronic interstitial lung diseases. While current therapies can slow disease progression, these strategies ultimately have a “low ceiling” in terms of clinical impact and are unlikely to halt or reverse disease. Using single-cell genomics, several researchers have recently identified multiple previously unrecognized cell types/states and cell type–specific dysregulation of gene expression in PF lungs. While impactful, these studies fail to capture the regional disease heterogeneity—a hallmark of PF.

To this end, researchers at Translational Genomics Research Institute (TGen) have carried out high-resolution, in situ spatial profiling on a total of 28 FFPE-preserved primary lung samples from seven healthy controls and 12 patients with PF. In total, they assayed 343 genes across 1.1 million cells and captured a total of 210 million transcripts. It became immediately clear that the cell-type composition inferred from this spatial in situ data matched much more closely with the biological “ground truth” when compared to methods requiring tissue dissociation (e.g. single cell RNA sequencing).

In particular, much higher proportions of fragile cell types, such as alveolar type I cells and endothelial cells, as well as cells deeply embedded in the extracellular matrix such as fibroblasts, were identified. In addition to identifying new signals of dysregulation, these analyses helped localize known signals at unprecedented granularity.

In this webinar, viewers will:

• Explore the power of image-based in situ spatial profiling and how it provides novel insights into the biology of pulmonary fibrosis
• Learn about how high-resolution, high-target in situ spatial analysis reveals cell-type composition that other methods may miss
• Understand how spatial niches defined by pathology-directed and unbiased clustering methods can be used to profile disease-associated cellular and molecular dysregulation in pulmonary fibrosis.