The expression of the HNF4 was negligible in the HWJMSCs cultured in all conditions; however, the cells cultured on 2D collagen film showed a non-significant increase in HNF4 expression compared to those cultured in conventional monolayer or 3D collagen scaffold (Figure 4).
(11) HNF4 can be considered as a gene with pivotal role in hepatocyte differentiation.
The real time RT-PCR detected a low level of the expression of HNF4 by HWJMSCs cultured on 2D collagen films.
However, the data from current study showed culturing the naive HWJMSCs in the presence of collagen led to a significant increase in some liver-specific markers, claudin but not CKs, albumin, AFP or HNF4. The increase in claudin expression may be attributed to the improvement of the cell-cell contact in a 3D environment.
In this case, transcription factors associated with the pancreas and liver were studied, leading the group to conclude that one specific transcription factor, HNF4
, controlled nearly half of all the genes used in the formation of the pancreas and liver.
Sigrist et al., "GATA6 regulates HNF4
and is required for differentiation of visceral endoderm in the mouse embryo," Genes & Development, vol.
For example, the PPAR response element used in the Attagene cis-PPRE reporter gene assay will bind PPAR[delta] and PPAR[alpha], RXR[alpha],[beta],[gamma], COUPTF[alpha],[beta], and HNF4
(Nakshatri and Bhat-Nakshatri 1998) at a minimum.
Bonzo et al., "The peroxisomal 3-keto-acyl-CoA thiolase B gene expression is under the dual control of PPAR and HNF4
in the liver," PPAR Research, vol.
Mature-Onset Diabetes Mellitus in Youth (MODY) and other forms of Diabetes have been genetically linked to the HNF4
Some of these scenarios are supported in a recent study where miRNAs were computationally predicted to target hepatic nuclear factor 4 [alpha] (HNF4
[alpha]) (Ramamoorthy et al.
Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4