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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
Nkx2-5 mediates differential cardiac differentiation through interaction with Hoxa10
Ann N Behrens1, Michelina Iacovino, Jamie L Lohr
1Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Stem Cells and Development
|March 13, 2013
Summary
Cardiac progenitor cells differentiate asynchronously, a process regulated by Nkx2-5. Posterior Hox genes, Hoxa9 and Hoxa10, show asymmetric expression and Hoxa10 impairs cardiac differentiation.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Genetics
Background:
- Cardiac differentiation is complex and Nkx2-5 has roles beyond cardiac development.
- Nkx2-5-positive cells contribute to multiple cell lineages.
- Transcriptional networks governing mesodermal patterning are not fully defined.
Purpose of the Study:
- To investigate the asynchronous differentiation of cardiac progenitor cells.
- To identify novel regulators of cardiac mesoderm differentiation.
- To elucidate the role of posterior Hox genes in cardiac development.
Main Methods:
- Profiling of early Nkx2-5-positive progenitor cells.
- Analysis of Nkx2-5 mutant embryos.
- Utilizing the embryonic stem cell/embryoid body (ES/EB) model system.
Main Results:
- Cardiac crescent progenitor pools differentiate asynchronously, dependent on Nkx2-5.
- Posterior Hox genes, Hoxa9 and Hoxa10, exhibit transient, asymmetric cardiac-specific expression.
- Hoxa10 was found to impair cardiac differentiation in the ES/EB model.
Conclusions:
- Asynchronous differentiation of cardiac progenitors is Nkx2-5-dependent.
- Posterior Hox genes Hoxa9 and Hoxa10 have a novel role in cardiac development.
- Hoxa10 may cooperate with Nkx2-5 to regulate cardiac mesoderm differentiation timing.
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