Spatial transcriptome profiling identifies CREB1 as a regulator of core transcriptional programs in idiopathic pulmonary fibrosis

A defining feature of idiopathic pulmonary fibrosis is the regional heterogeneity of the lung pathology. Here we established methodology to study the transcriptome of spatially discrete morphological areas in IPF lung tissue through the integration of laser capture microdissection of formalin fixed paraffin embedded lung tissue with low input RNA-Seq. We applied this methodology to obtain an in situ transcriptome for fibroblast foci and alveolar septae from IPF tissue as well as alveolar septae from age sex-matched control lung tissue. Differential gene expression analysis was performed between IPF alveolar septae vs control alveolar septae and between IPF fibroblast foci vs alveolar epithelium. Metacore TM was used for gene enrichment analysis of significantly differentially expressed genes, for transcription factor (TF) network analysis to identify predicted TF from human TF-target gene interaction. Overall design: Laser capture microdissection was performed upon formalin fixed paraffin embedded (FFPE) control non-fibrotic lung tissue (alveolar septae (n=10)) and UIP/IPF FFPE lung tissue (myofibroblast foci, (n=10) and adjacent non-affected alveolar septae (n=10)).