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Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction
Published on: November 3, 2011
hhLIM is involved in cardiomyogenesis of embryonic stem cells
Bin Zheng1, Jin-Kun Wen, Mei Han
1Hebei Laboratory of Medical Biotechnology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Insights
hhLIM is a potent transcriptional activator crucial for cardiomyocyte differentiation. Its inhibition blocks cardiac development, while overexpression enhances cardiac marker gene expression and promotes cardiomyocyte-like morphology.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cardiology
Background:
- Proteins of the LIM family are vital for biological processes like cell lineage specification and organ development.
- Understanding the role of novel LIM family members in cardiac development is essential.
Purpose of the Study:
- To investigate the function of hhLIM in cardiogenesis.
- To analyze the molecular mechanisms underlying hhLIM's role in cardiomyocyte differentiation.
Main Methods:
- Molecular analysis of hhLIM-deficient P19 cell lines.
- Studying P19 cells with stable hhLIM overexpression.
- Utilizing antisense transcripts to inhibit hhLIM expression.
Main Results:
- hhLIM acts as a potent transcriptional activator of cardiac muscle-specific genes.
- Inhibition of hhLIM expression disrupts cardiac gene expression and blocks beating cardiomyocyte development.
- Overexpression of hhLIM enhances cardiac marker genes (Nkx2.5, GATA-4) and promotes cardiomyocyte morphology.
Conclusions:
- hhLIM is critical for activating the cardiac genetic program.
- hhLIM may serve as a nuclear target for inductive factors in precardiac cells.
Abstract:
Proteins of the LIM family play important roles in a variety of fundamental biological processes including cell lineage specification and organ development. Here we examined the function in cardiogenesis of a new member of the LIM family, hhLIM, by molecular analysis of early stages of cardiomyocyte differentiation in hhLIM-deficient P19 cell line and P19 cells stably overexpressing hhLIM. The results indicate that hhLIM is a potent transcriptional activator of several cardiac muscle-specific genes. Inhibition of hhLIM expression by antisense transcripts can interfere with expression of cardiac muscle genes and block development of beating cardiomyocytes in P19 embryonic stem cells. Overexpression of hhLIM in P19 cells can enhance expression of cardiac marker genes Nkx2.5 and GATA-4 and potentiate development of cardiomyocyte-like morphology. These findings suggest that, in addition to its role in activation of the cardiac genetic program, hhLIM may be the nuclear target of inductive factor for precardiac cells.
