Single cell RNA-seq revealed critical genetic programs of invasive fibroblasts for pulmonary fibrosis

We performed a single cell RNA-seq survey of 14,704 invasive fibroblasts and 16,104 non-invasive fibroblasts using an in vitro assay system which had been previously used to evaluate the ability of lung fibroblasts to spontaneously invade Matrigel and commonly used to analyze the metastatic potential of cancer cells. Different subtypes in invasive or non-invasive lung fibroblasts were classified, and their gene signatures, specific cell surface markers, long non-coding RNA (lncRNA), key transcription factors and signaling pathways were further confirmed mechanistically and functionally. After combination of all the specific genes for Ingenuity Pathway Analysis (IPA), we found that the ERBB2 (HER2) signaling pathway was significantly activated in invasive fibroblasts and was markedly inhibited in non-invasive fibroblasts. Overall design: Profiling invasive and non-invasive fibroblasts of lung fibroblasts from Idiopathic pulmonary fibrosis