Phosphoinositide 3 Kinase Signaling in Human Stem Cells from Reprogramming to Differentiation: A Tale in Cytoplasmic and Nuclear Compartments

Abstract

Stem cells are undifferentiated cells that can give rise to several different cell types and can self-renew. Given their ability to differentiate into different lineages, stem cells retain huge therapeutic potential for regenerative medicine. Therefore, the understanding of the signaling pathways involved in stem cell pluripotency maintenance and differentiation has a paramount importance in order to understand these biological processes and to develop therapeutic strategies. In this review, we focus on phosphoinositide 3 kinase (PI3K) since its signaling pathway regulates many cellular processes, such as cell growth, proliferation, survival, and cellular transformation. Precisely, in human stem cells, the PI3K cascade is involved in different processes from pluripotency and induced pluripotent stem cell (iPSC) reprogramming to mesenchymal and oral mesenchymal differentiation, through different and interconnected mechanisms.

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

“…The interaction between osteopontin and integrin αv/β1 induced osteogenesis and inhibited adipogenesis in MSCs [ 56 ]. Therefore, the binding of osteopontin, fibronectin, and other molecules involved in osteogenic differentiation could determine the possible balance between MSCs that commit toward adipogenic or osteogenic differentiation [ 57 ]. We have observed the upregulation of cadherin 11 (CDH11) on all 3 days.…”

Phosphoinositide-Dependent Signaling in Cancer: A Focus on Phospholipase C Isozymes

“…All these cellular processes are consistent with the hallmarks of cancer. Furthermore, PI levels are regulated by several lipid kinases, phosphatases and phospholipases in response to different external stimuli, with a plethora of studies showing that a deregulation of the PI metabolism mediated by these enzymes is implicated in several diseases [12][13][14].…”

Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases

“…Moreover, DGKs θ and ζ are found at the plasma membrane upon activation of some G protein-coupled receptors (Table 1) [73,74]. Several studies showed that the nuclear inositide signaling is involved in regulating essential cellular processes, such as cell cycle and differentiation [75][76][77][78], while it is also implicated in several pathologies, including myelodysplastic syndromes, brain diseases, and cancer [79][80][81][82]. Interestingly, DGKs, which have been discovered in nearly all cell compartments, were also found in the nucleus.…”