Lowering the increased intracellular pH of human-induced pluripotent stem cell‐derived endothelial cells induces formation of mature Weibel‐Palade bodies
Gesa L. Tiemeier, et al., STEM CELLS Translational Medicine
The formation of functional and mature Weibel-Palade bodies (WPBs), essential for endothelial cell (EC) function, in human induced pluripotent stem cell (hiPSC)-ECs is a crucial step in the development of the full potential of hiPSC-EC for tissue regeneration, organ vascularization, and disease modeling. The results of this study show that hiPSC-ECs have a higher intracellular pH (pHi) than mature EC, where pro-VWF dimers require the lower pH environment for maturation and tubulation. In addition, decreased expression of MCT1, a pHi-sensitive member of the solute carrier family (SLC16A1), which regulates lactate and H+ uptake was observed. By lowering pHi with acetic acid, formation of mature WPBs in hiPSC-ECs could be induced.
In the adult brain, to maintain a continuous supply of new neurons and to avoid the exhaustion of the neural stem cells (NSCs) pool, a tight control between quiescence and proliferation is crucial. The inhibitor of DNA binding 1 (id1) gene controls the balance between dividing and resting neural stem cells by promoting quiescence. A regulatory sequence of id1 was identified, which mediates the input from the bone morphogenetic protein signaling into the adult NSCs. This regulatory sequence has a high potential to serve as an interface, which will permit to alter the balance between proliferation and maintenance of stem cells in experimental, as well as medical, applications.
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Lowering the intracellular pH can induce the maturation of endothelial cells derived from human induced pluripotent stem cells and hence enhance their regenerative potential