Several neurohormones have been identified in decapod precardiac
organs, which are ideally located to release their products in hemolymph on its bypass to the heart (Alexandrowicz, 1953), which include serotonin, dopamine, and octopamine (Beltz & Kravitz, 1983); this last one relaxes the anterior cardio-arterial muscle and causes contraction of the posterior valve in lobster, and it changes hemolymph distribution toward the anterior arterial system in crabs (Airries & McMahon, 1994).
Bone marrow mesenchymal stem cells (MSCs) treated with BIX01294 showed an induced expression of Mesp1 and brachyury [13, 14], which are markers associated with precardiac progenitors in the early embryo [15-17].
When these iPSC helper molecules were tested for their ability to broaden the potential of bone marrow stem cells, the only one that appreciably upregulated precardiac markers and allowed the cells to respond to cardiogenic signals was the G9a HMTase inhibitor BIX01294.
The above results indicated that TSA synergistically enhanced the induced expression by BIX01294 of key transcription factors characteristic of embryonic precardiac progenitors (Figures 1 and 2).
Our previous investigations have demonstrated that the G9a HMTase inhibitor BIX01294 will cause these cells to exhibit the early mesodermal, precardiac markers Mesp1 and brachyury, without any corresponding enhancement of either endodermal, ectodermal, or pluripotency markers .
In that regard, experiments using MOCPAC or BATCP--which are preferential inhibitors of class I or II HDACs, respectively --generated results similar to TSA in enhancing BIX01294 stimulation of precardiac gene expression (not shown).