Abstract:Since the Japanese scientist Shinya Yamanaka used a viral vector to transfer the combination of 4 factors into differentiated somatic cells and reprogramed them to obtain similar embryonic stem cells and induced pluripotent stem cells (iPSCs), it provided one integrative method for studying many medical fields. Patient-derived iPSCs have provided an opportunity to study human diseases for which no suitable model systems are available. iPSC technology has since become a major breakthrough in the field of stem c… Show more
“…Human iPSCs have been generated from various cell types and have a great potential for regenerative medicine, because they enable the derivation of patient‐specific pluripotent cells and serve as a platform for stem‐based research, disease modeling, and drug discovery/repurposing . Despite extensive research toward understanding of the reprogramming process, the underlying mechanisms are not fully understood , hindering their effective application in clinical studies . A number of molecular and cellular barriers of reprogramming have been identified to date , resulting in an overall 2%–5% efficiency, thus indicating that the majority of cells are unable to complete reprogramming toward pluripotency .…”
Direct reprogramming of human somatic cells toward induced pluripotent stem cells holds great promise for regenerative medicine and basic biology. We used a high‐throughput small interfering RNA 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 signaling pathway during somatic cell‐induced reprogramming. Downregulation of one of the key GPCR effectors, endothelial differentiation GPCR5 (EDG5), impacted the maintenance of pluripotency, actin cytoskeleton organization, colony integrity, and focal adhesions in human embryonic stem cells, which were associated with the alteration in the RhoA‐ROCK‐Cofilin‐PAXILLIN‐actin signaling 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 colony integrity, and a significant reduction in partially 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 of EDG5 in the maintenance and acquisition of pluripotency. Stem Cells 2019;37:318–331
“…Human iPSCs have been generated from various cell types and have a great potential for regenerative medicine, because they enable the derivation of patient‐specific pluripotent cells and serve as a platform for stem‐based research, disease modeling, and drug discovery/repurposing . Despite extensive research toward understanding of the reprogramming process, the underlying mechanisms are not fully understood , hindering their effective application in clinical studies . A number of molecular and cellular barriers of reprogramming have been identified to date , resulting in an overall 2%–5% efficiency, thus indicating that the majority of cells are unable to complete reprogramming toward pluripotency .…”
Direct reprogramming of human somatic cells toward induced pluripotent stem cells holds great promise for regenerative medicine and basic biology. We used a high‐throughput small interfering RNA 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 signaling pathway during somatic cell‐induced reprogramming. Downregulation of one of the key GPCR effectors, endothelial differentiation GPCR5 (EDG5), impacted the maintenance of pluripotency, actin cytoskeleton organization, colony integrity, and focal adhesions in human embryonic stem cells, which were associated with the alteration in the RhoA‐ROCK‐Cofilin‐PAXILLIN‐actin signaling 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 colony integrity, and a significant reduction in partially 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 of EDG5 in the maintenance and acquisition of pluripotency. Stem Cells 2019;37:318–331
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