| Autor: |
Kyung Tae Lim, Seung Chan Lee, Yimeng Gao, Kee-Pyo Kim, Guangqi Song, Su Yeon An, Kenjiro Adachi, Yu Jin Jang, Jonghun Kim, Kyoung-Jin Oh, Tae Hwan Kwak, Seon In Hwang, Jueng Soo You, Kinarm Ko, Seung-Hoi Koo, Amar Deep Sharma, Jong-Hoon Kim, Lijian Hui, Tobias Cantz, Hans R. Schöler, Dong Wook Han |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 15, Iss 4, Pp 814-829 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2016.03.071 |
| Popis: |
Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps). However, reported conversion efficiencies are very low, and the underlying mechanism of the direct hepatic reprogramming is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving the erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Through screening for additional factors that could potentially enhance the conversion kinetics, we have found that c-Myc and Klf4 (CK) dramatically accelerate conversion kinetics, resulting in remarkably improved iHep generation. Furthermore, we identified small molecules that could lead to the robust generation of iHeps without CK. Finally, we show that Hnf1α supported by small molecules is sufficient to efficiently induce direct hepatic reprogramming. This approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into the clinic. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
