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Isolation of CD133+ Liver Stem Cells for Clonal Expansion
Published on: October 10, 2011
MBD3 inhibits formation of liver cancer stem cells
Ruizhi Li1, Qihua He1, Shuo Han1
1Stem Cell Research Center, Department of Cell Biology, School of Basic Medical Sciences, Peking University, Haidian District, Beijing, 100191, China.
Abstract:
Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells. Expression of the transcription factor c-JUN is increased in MBD3-depleted iCSCs, and c-JUN activates endogenous pluripotent genes and regulates iCSC-related genes. These results indicate that MBD3/NuRD inhibits the induction of iCSCs, while c-JUN facilitates the generation of CSC-like properties. The iCSC reprogramming approach devised here provides a novel platform for dissection of the disordered signaling in liver CSCs. In addition, our results indicate that c-JUN may serve as a potential target for liver cancer therapy.
Insights
Liver cancer cells can become stem-like cells (iCSCs) when key factors are manipulated. Suppressing MBD3 and using OSKM factors promotes this conversion, with c-JUN playing a key role in generating CSC-like properties.
Area of Science:
- Cancer Biology
- Stem Cell Research
- Epigenetics
Background:
- Liver cancer stem cells (CSCs) are crucial for tumor growth and recurrence.
- The nucleosome remodeling and deacetylase (NuRD) complex plays a role in cell reprogramming.
- Induced CSCs (iCSCs) can be generated from cancer cells using specific transcription factors.
Purpose of the Study:
- To investigate the role of the NuRD complex in the induction of liver CSCs.
- To explore the potential of MBD3 suppression in generating iCSCs.
- To identify key transcription factors involved in iCSC generation.
Main Methods:
- Exogenous expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) in liver cancer cells.
- Suppression of methyl-CpG binding domain protein 3 (MBD3), a NuRD complex subunit.
- Analysis of gene expression changes, including transcription factor c-JUN and pluripotent genes.
Main Results:
- Suppression of MBD3 along with OSKM transduction successfully converted liver cancer cells into stem-like cells.
- MBD3 depletion led to increased expression of the transcription factor c-JUN.
- c-JUN was found to activate endogenous pluripotent genes and regulate iCSC-related genes.
Conclusions:
- The MBD3/NuRD complex inhibits the induction of iCSCs, while c-JUN promotes CSC-like properties.
- This study presents a novel platform for studying liver CSC signaling.
- c-JUN emerges as a potential therapeutic target for liver cancer treatment.
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