Transcription factor-mediated reprograming of fibroblasts to hepatocyte-like cells
| Autor: | Hossein Baharvand, Behshad Pournasr, Mohammad Hassan Asghari-Vostikolaee |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cell type
Histology Cell Biology Regenerative medicine Pathology and Forensic Medicine Mice CEBPA medicine Animals Humans Secretion Transcription factor Cell Shape Hepatocyte differentiation Cell Biology General Medicine Fibroblasts Cellular Reprogramming Cell biology Culture Media medicine.anatomical_structure HEK293 Cells Biochemistry Hepatocyte Cell Transdifferentiation Hepatocytes Glycogen Transcription Factors |
| Zdroj: | European journal of cell biology. 94(12) |
| ISSN: | 1618-1298 |
| Popis: | Direct conversion by overexpression of defined transcription factors (TFs) is a promising new method that can generate desired cell types from abundant, accessible cells. While previous studies have reported hepatic generation from fibroblasts, tremendous interest exists in the understanding of hepatic reprograming and its applicability in regenerative medicine. Here, we show that overexpression of Yamanaka factors can induce reprograming of mouse fibroblasts into cells that closely resemble hepatocytes in vitro in the presence of an optimized hepatic growth medium. By screening the effects of 20 candidate transcription factors, we identified a combination of three TFs (Hnf4a, Cebpa, and Nr1i2) that can convert fibroblasts into a hepatic fate. These factors in conjunction with Yamanaka factors increase the efficiency of hepatic reprograming. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific characteristics; express hepatocyte-specific markers, glycogen storage, albumin secretion, urea production, as well as low-density lipoprotein and indocyanin green uptake. Production of iHep cells by these novel approaches may bring new insights into the molecular nature of hepatocyte differentiation and future cell-based therapeutics for liver diseases. |
| Databáze: | OpenAIRE |
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