논문 상세보기
Direct Conversion of Fibroblasts into Hepatocytes By Defined Factors
- 언어ENG
- URLhttps://db.koreascholar.com/Article/Detail/213381
Recent advances in stem cell biology have shown that terminally differentiated somatic cells can be directly converted to the different types of somatic cells such as neurons and cardiomyocytes with defined sets of transcription factors without going through a pluripotent state. Recently, it was demonstrated that the hepatocyte-specific transcription factors, Hnf4α plus Foxa1, Foxa2 or Foxa3 could erase somatic memory and reset hepatocyte program on the differentiated somatic genome. Here, we show that Foxa3 together with Hnf4α could efficiently reprogram fibroblasts into hepatocytes. However, the direct conversion into hepatocytes is not observed with Hnf4α plus Foxa1. After two weeks of retroviral transduction of Hnf4α and Foxa3, we observed epithelial colonies emerged from starting fibroblasts and were able to establish stable hepatocyte cell lines, namely induced hepatocytes (iHep cells). The iHep cells closely resemble primary hepatocytes in a number of characteristics such as their polygonal shapes, the hepatic gene expression patterns and the presence of E-cadherin signals as determined by immunocytochemistry. In addition, iHep cells show the storage of glycogen as revealed by Periodic acid-Schiff (PAS) staining, indicating that iHep cells are functionally similar to their in vivo counterparts. Taken together, our findings suggest that the combination of hepatic transcription factors, Hnf4α with Foxa3 but not Foxa1 could induce hepatocyte fate on the differentiated somatic cells.
