Chromatin state analysis of HUVECs and those transduced with hiHepPC-inducing factors in culture with or without CHIR99021 [ATAC-seq]

We previously showed that a specific combination of three transcription factors (FOXA3, HNF1A, and HNF6) can induce direct reprogramming of human umbilical vein endothelial cells (HUVECs) and peripheral blood-derived endothelial cells into human induced hepatic progenitor cells (hiHepPCs; PMID: 33087715). However, the low induction efficiency of hiHepPCs will be a problem when using them in research and clinical applications. Here, we show that activation of the canonical Wnt signaling pathway increase the reprogramming efficiency of HUVECs to hiHepPCs by rapidly inducing chromatin remodeling and gene expression changes in the transduced HUVECs. Overall design: hiHepPCs were induced from HUVECs by forced expression of the three transcription factors (FOXA3, HNF1A, and HNF6). ATAC-seq was performed 9, 16, and 44 days after retrovirus infection. Two conditions, with and without CHIR99021, were examined during induction of hiHepPCs from HUVECs. Additionally, the same analysis was conducted for parental HUVECs.