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Rho/ROCK pathway is essential for the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acidFrisca Frisca,* Duncan E. Crombie,*, Mirella Dottori,Yona Goldshmit,,** and Alice P ay1,*,Department of Ophthalmology,* University of Melbourne, East Melbourne VIC, Australia; Centre for Eye Research, Australia Royal Victorian Eye and Ear Hospital, East Melbourne VIC, Australia; Department of Anatomy and Neurosciences,University of Melbourne, Parkville VIC, Australia; and Australian Regenerative Medicine Institute,** Monash University, Clayton, VIC, AustraliaAbstract We previously reported that lysophosphatidic acid (LPA) inhibits the neuronal differentiation of human embryonic stem cells (hESC).Emamectin Epigenetic Reader Domain We extended these studies by analyzing LPA’s effects on the expansion of neural stem/ progenitor cells (NS/PC) derived from hESCs and human induced pluripotent stem cells (iPSC), and we assessed no matter if data obtained on the neural differentiation of hESCs had been relevant to iPSCs.c-di-AMP custom synthesis We showed that hESCs and iPSCs exhibited comparable mRNA expression profiles of LPA receptors and producing enzymes upon neural differentiation.PMID:24635174 We demonstrated that LPA inhibited the expansion of NS/PCs of each origins, mainly by enhanced apoptosis inside a Rho/Rho-associated kinase (ROCK)-dependent mechanism. Additionally, LPA inhibited the neuronal differentiation of iPSCs. Lastly, LPA induced neurite retraction of NS/ PC-derived early neurons through Rho/ROCK, which was accompanied by myosin light chain (MLC) phosphorylation. Our information demonstrate the consistency of LPA effects across many sources of human NS/PCs, rendering hESCs and iPSCs beneficial models for studying lysophospholipid signaling in human neural cells. Our information also highlight the significance in the Rho/ROCK pathway in human NS/ PCs. As LPA levels are improved in the central nervous program (CNS) following injury, LPA-mediated effects on NS/ PCs and early neurons could contribute to the poor neurogenesis observed inside the CNS following injury.–Frisca, F., D. E. Crombie, M. Dottori, Y. Goldshmit, as well as a. P ay. Rho/ROCK pathway is essential towards the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid. J. Lipid Res. 2013. 54: 1192206.Supplementary key.
