Description
Liver fibrosis usually involve different cell types interaction. Despite its devastating consequences, there are no treatments for liver fibrosis. Genome engineering and a human hepatic organoid system was used to produce the first nave in vitro model including several crucial components contributed for liver fibrosis. Hepatic organoids engineered to express the most common causative mutation for Autosomal Recessive Polycystic Kidney Disease (ARPKD) developed abnormal bile ducts and hepatic fibrosis in only 21 days, which are the key features of ARPKD liver pathology. Singel cell level analysis indicated that the ARPKD mutation induced bile duct proliferation through several critial pathways, and appear to be actively involved in collagen fiber generation. Therefore, abnormal cholangiocytes promotes the expansion its counterpart , which collagen-producing myofibroblasts with a markedly increased level of PDGFRB protein expression and evidence of an activated STAT3 signalling pathway.
Overall Design
To study transcriptomic changes during iPSC-HB-HOs differentiation between control and ARPKD, Firstly, we compared 3 control vs 3 ARPKD donors at HO stage; then we compared those paires at all iPSC-HB-HO stages using 10x Chromium based single cells RNA-seq platform. We used ‘demuxlet’ and cell hashing pipeline to multiplex sample input for single cell RNA-seq, which rely on decode genetic variation and cell labeling respectively.
Curator
xm_li