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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
HEXIM1 induces differentiation of human pluripotent stem cells
Vanessa Ding1, Qiao Jing Lew, Kai Ling Chu
1Stem Cell Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
Plos One
|August 27, 2013
Summary
Hexamethylene bisacetamide inducible protein 1 (HEXIM1) regulates human pluripotent stem cell (hPSC) fate. Increased HEXIM1 protein levels promote hPSC differentiation via a pathway independent of positive transcription elongation factor b (P-TEFb).
Area of Science:
- Stem cell biology
- Molecular biology
- Gene regulation
Background:
- Hexamethylene bisacetamide inducible protein 1 (HEXIM1) inhibits positive transcription elongation factor b (P-TEFb), a key regulator of transcriptional elongation.
- Most mRNA synthesis is regulated at the transcription elongation stage, suggesting a role for P-TEFb/HEXIM1 in stem cell gene regulation.
Purpose of the Study:
- To investigate the role of HEXIM1 in the differentiation of human pluripotent stem cells (hPSCs).
- To determine if P-TEFb activity is required for hPSC differentiation.
Main Methods:
- Treatment of hPSCs with LY294002 to induce differentiation and observe HEXIM1 protein levels.
- Assessing changes in CDK9 and cyclin T1 levels.
- Treatment with P-TEFb inhibitor flavopiridol.
- Incubation of hPSCs with hexamethylene bisacetamide.
- Overexpression of HEXIM1 in hPSCs.
Main Results:
- LY294002 treatment markedly increased HEXIM1 protein levels in differentiated hPSCs without altering CDK9 or cyclin T1.
- Flavopiridol, a P-TEFb inhibitor, did not induce hPSC differentiation.
- Hexamethylene bisacetamide and HEXIM1 overexpression both induced hPSC differentiation.
Conclusions:
- HEXIM1 plays a novel role in regulating hPSC fate.
- hPSC differentiation can be regulated by HEXIM1 through a P-TEFb-independent pathway.
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