Fibroblasts

To study interferon response in human fibroblasts by analysing the transcriptional changes following stimulation with dsRNA (Poly I:C) and interferon beta in 100 cell lines. Pooled cell populations were then analysed using single cell sequencing (10x) to analyse transcription responses following stimulation.

The interferon type I immune response acts as a central regulator to restrict pathogen propagation and alert the adaptive immune system. This response, however, is not well characterised, despite its importance in many infectious diseases, cancer and autoimmune diseases. It is unclear how the response differs between individuals from different genetic backgrounds.

The project aimed to address these two main questions:

(1) How does the interferon response vary between different human individuals with different genetic backgrounds?

(2) How do different individual cells respond to a danger signal (dsRNA) that should elicit interferon, and how do they respond to a direct interferon stimulus?

The response was studied in skin fibroblast cells from 100 donors from the HipSci project. The interferon response was initiated using dsRNA transfection, as well as by direct stimulation with IFNbeta. This was used to characterise single cell response and grown in heterogeneous populations composed of cells from various individuals.