Abstract

Spatial transcriptomic technologies using barcoding were developed to capture the spatial coordinates of mRNA transcripts in an unbiased manner. We investigated the abnormal signaling that occurred in the airways from IPF lung.

We conducted spatial Visium technology (10X Genomics) on frozen fibrotic lung tissue obtained from 12 IPF patients and 4 control patients.  Using DESTVI, we deconvoluted this Spatial dataset, using our own ScRNAseq dataset. We used NICHES, to investigate signaling mechanisms specific to each cellular niche.

32 000 spot were analyzed. All the major compartment of lungs were identified. (Figure 1A). . Spots designed as Airway_ injury showed a significative increase of genes expressed by Aberrant Basaloid cells  such as KRT17, CTSE or MMP7 (figure 1B).Airway_injury niches (in grey) were closely located to the airway (orange) and to the alveoli (green) (Figure 1C).  The ligand receptor analysis (figure 1B) suggest that airway_injury niche shared some signaling mechanism with airway_niche through MDK_TSPAN axis (Figure 1D).At the spot level, observed a positive correlation between the proportion of Aberrant basaloid Cells , ATII, ATI and  basal cells (Figure 1E, 1F)

Our signaling analysis suggest a potential communication between different adjacent niches. This result needs to be validated in larger group of samples and at cellular level.