Liver X receptor α (LXRα/NR1H3) regulates differentiation of hepatocyte-like cells via reciprocal regulation of HNF4α.
J Hepatol
; 61(6): 1276-86, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25073010
ABSTRACT
BACKGROUND & AIMS:
Hepatocyte-like cells, differentiated from different stem cell sources, are considered to have a range of possible therapeutic applications, including drug discovery, metabolic disease modelling, and cell transplantation. However, little is known about how stem cells differentiate into mature and functional hepatocytes.METHODS:
Using transcriptomic screening, a transcription factor, liver X receptor α (NR1H3), was identified as increased during HepaRG cell hepatogenesis; this protein was also upregulated during embryonic stem cell and induced pluripotent stem cell differentiation.RESULTS:
Overexpressing NR1H3 in human HepaRG cells promoted hepatic maturation; the hepatocyte-like cells exhibited various functions associated with mature hepatocytes, including cytochrome P450 (CYP) enzyme activity, secretion of urea and albumin, upregulation of hepatic-specific transcripts and an increase in glycogen storage. Importantly, the NR1H3-derived hepatocyte-like cells were able to rescue lethal fulminant hepatic failure using a non-obese diabetic/severe combined immunodeficient mouse model.CONCLUSIONS:
In this study, we found that NR1H3 accelerates hepatic differentiation through an HNF4α-dependent reciprocal network. This contributes to hepatogenesis and is therapeutically beneficial to liver disease.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Diferenciação Celular
/
Hepatócitos
/
Fator 4 Nuclear de Hepatócito
/
Receptores Nucleares Órfãos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article