Abstract:
: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.
journal_name
Eur J Cell Bioljournal_title
European journal of cell biologyauthors
Pournasr B,Asghari-Vostikolaee MH,Baharvand Hdoi
10.1016/j.ejcb.2015.10.003subject
Has Abstractpub_date
2015-12-01 00:00:00pages
603-10issue
12eissn
0171-9335issn
1618-1298pii
S0171-9335(15)30013-3journal_volume
94pub_type
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doi:
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