The role of Lgr5+ cells in TNF-induced HF TAT was further validated by specifically knocking down TNFR1 in Lgr5+ cells with shRNA, which markedly reduced TNF-induced p-AKT activity in cultured Lgr5+ cells derived from Lgr5-EGFP mice (Supplementary Fig. 6c). This evidence concerns the gene LGR5 and hydrops fetalis.