Fig. 5: HNF1A^+/H126D mutation reduces the expression of genes involved in pancreas development, β cell survival and insulin secretion.

a RT-qPCR analysis of TM4SF4, GLIS3, ANKS4B, HNF4A, TSPAN8 and UGT2B4 transcripts in WT (red) and mutant (blue) hPSC-derived endocrine progenitors. n = 3 independent experiments. P-value for TM4SF4 = 0.0238 (P1), 0.0390 (P2); GLIS3 = 0.0239 (P1), 0.0184 (P2); ANKS4B = 0.0081 (P1), 0.0260 (P2); HNF4A = 0.0385 (P1), 0.0449 (P2); TSPAN8 = 0.0112 (P1), 0.0355 (P2); UGT2B4 = 0.0020 (P1), 0.0130 (P2). b RT-qPCR analysis of EndoC-βH1 cells transfected with HNF1A siRNA (si-HNF1A) and non-targeting siRNA as negative control (si-NT). n = 4 independent experiments. P-value for TM4SF4 = 0.0029; GLIS3 = 0.0240; ANKS4B = 0.0017; HNF4A = 0.0172; UGT2B4 = 0.0226. c Western blot analysis for HNF1A protein in AD-293 cells overexpressed with GFP and various HNF1A constructs. n = 3 independent experiments. d RT-qPCR analysis of TM4SF4, GLIS3, ANKS4B, HNF4A, TSPAN8 and UGT2B4 transcripts in AD-293 cells overexpressed with GFP (green) and various WT (red), H126D (blue) and P291fsinsC (purple) HNF1A constructs. n = 3 independent experiments. P-value for TM4SF4 = 0.0076 (WT), 0.0078 (H126D), 0.0077 (P291fsinsC); GLIS3 = 0.0005 (WT), 0.0121 (H126D), 0.0171 (P291fsinsC); ANKS4B = 0.0005 (WT), 0.0004 (H126D); HNF4A: 0.0026 (WT), 0.0078 (H126D), 0.0886 (P291fsinsC); TSPAN8 = 0.0015 (WT), 0.0034 (H126D), 0.0005 (P291fsinsC); UGT2B4 = 0.0035 (WT), 0.0034 (H126D), 0.0035 (P291fsinsC). WT wild-type, P1 patient 1, P2 patient 2. GFP green fluorescent protein. RT-qPCR quantitative reverse transcription polymerase chain reaction. hPSC human pluripotent stem cells. For all statistical analysis: Error bars represent standard error of mean (SEM). Unpaired one-tailed Student’s t-test was performed. Asterisk indicates P-value < 0.05. n.s. non-significant. “See also Fig. S7.” Source data are provided as a Source data file.