EDG5 plays an important role in induction and maintenance of pluripotency

Graphical abstract summarizing the main findings generated from this study. AbstractDirect reprogramming of human somatic cells toward induced pluripotent stem cells holds great promise for regenerative medicine and basic biology. We used a high ‐throughput siRNA screening assay in the initiation phase of reprogramming for 784 genes belonging to kinase and phosphatase families and identified 68 repressors and 22 effectors. Six new candidates belonging to the family of the G protein–coupled receptors (GPCRs) were identified suggesting an important role for this key signalling pathway during somatic cell induced reprogramming. Downregulation of one of the key GPCR effectors,EDG5 impacted the maintenance of pluripotency, actin cytoskeleton organisation, colony integrity and focal adhesions in human embryonic stem cells (hESCs) which were associated with the alteration in the RhoA ‐Rock‐Cofilin‐Paxillin‐actin signalling pathway. Similarly, downregulation of EDG5 during the initiation stage of somatic cell induced reprogramming resulted in alteration of cytoskeleton, loss of human induced pluripotent stem cell (hiPSC) colony integrity and a significant reduction in par tially and fully reprogrammed cells as well as the number of alkaline phosphatase positive colonies at the end of the reprogramming process. Together these data point to an important role for EDG5 in maintenance and acquisition of pluripotency.© AlphaMed Press 2018
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research