|標題:||DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells|
Ho, Jennifer H.
Yang, Vincent W.
Lee, Oscar K.
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
Center for Bioinformatics Research
|摘要:||The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor beta 1 (TGF beta 1), which in turn controls hepatogenic differentiation and de-differentiation. In addition, a stepwise reduction in TGF beta 1 concentrations in culture media increases DNMT1 and decreases DNMT3 in primary hepatocytes (Heps) and confers Heps with multi-differentiation potentials similarly to MSCs. Hepatic lineage reversibility of MSCs and lineage conversion of Heps are regulated byDNMTs in response to TGF gamma 1. This previously unrecognized TGF beta 1-DNMTs-MSC-HD axis may further increase the understanding the normal and pathological processes in the liver, as well as functions of MSCs after transplantation to treat liver diseases.|
|期刊:||STEM CELL REPORTS|
|Appears in Collections:||Articles|
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