Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13287-018-1061-4
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dc.titleThe prostaglandin H2 analog U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways
dc.contributor.authorSu, L.
dc.contributor.authorKong, X.
dc.contributor.authorLim, S.
dc.contributor.authorLoo, S.
dc.contributor.authorTan, S.
dc.contributor.authorPoh, K.
dc.contributor.authorDutton, J.
dc.contributor.authorStewart, C.
dc.contributor.authorCook, S.
dc.contributor.authorSu, X.
dc.contributor.authorMa, J.
dc.contributor.authorZhang, J.
dc.contributor.authorYe, L.
dc.date.accessioned2020-09-07T05:01:53Z
dc.date.available2020-09-07T05:01:53Z
dc.date.issued2018
dc.identifier.citationSu, L., Kong, X., Lim, S., Loo, S., Tan, S., Poh, K., Dutton, J., Stewart, C., Cook, S., Su, X., Ma, J., Zhang, J., Ye, L. (2018). The prostaglandin H2 analog U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways. Stem cell research & therapy 9 (1) : 313. ScholarBank@NUS Repository. https://doi.org/10.1186/s13287-018-1061-4
dc.identifier.issn17576512
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174517
dc.description.abstractBACKGROUND: We have shown that the differentiation of human-induced pluripotent stem cells (hiPSCs) into endothelial cells (ECs) is more efficient when performed with a 3-dimensional (3D) scaffold of biomaterial than in monolayers. The current study aims to further increase hiPSC-EC differentiation efficiency by deciphering the signaling pathways in 3D scaffolds. METHODS AND RESULTS: We modified our 3D protocol by using U-46619 to upregulate both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, which increased the differentiation efficiency (as measured by CD31 expression) to as high as 89% in two established hiPSC lines. The differentiated cells expressed arteriovenous, but not lymphatic, markers; formed tubular structures and EC lumen in vitro; had significantly shorter population-doubling times than monolayer-differentiated hiPSC-ECs; and restored perfusion and vascularity in a murine hind limb ischemia model. The differentiation efficiency was also>?85% in three hiPSC lines that had been derived from patients with diseases or disease symptoms that have been linked to endothelial dysfunction. CONCLUSIONS: These observations demonstrate that activating both p38MAPK and ERK1/2 signaling pathways with U-46619 improves the efficiency of arteriovenous hiPSC-EC differentiation and produces cells with greater proliferative capacity.
dc.publisherBioMed Central Ltd.
dc.sourceUnpaywall 20200831
dc.subject15 hydroxy 11alpha,9alpha epoxymethanoprosta 5,13 dienoic acid
dc.subject6 [[2 [[4 (2,4 dichlorophenyl) 5 (4 methyl 1h imidazol 2 yl) 2 pyrimidinyl]amino]ethyl]amino]nicotinonitrile
dc.subjectmitogen activated protein kinase p38
dc.subjectpyridine derivative
dc.subjectpyrimidine derivative
dc.subjectanimal
dc.subjectcell differentiation
dc.subjectcell line
dc.subjectcytology
dc.subjectdisease model
dc.subjectdrug effect
dc.subjectendothelium cell
dc.subjectenzyme activation
dc.subjectenzymology
dc.subjecthindlimb
dc.subjecthuman
dc.subjectinduced pluripotent stem cell
dc.subjectischemia
dc.subjectMAPK signaling
dc.subjectmesoderm
dc.subjectmetabolism
dc.subjectnonobese diabetic mouse
dc.subjectpathology
dc.subjectperfusion
dc.subjectSCID mouse
dc.subjectvascularization
dc.subject15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
dc.subjectAnimals
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectDisease Models, Animal
dc.subjectEndothelial Cells
dc.subjectEnzyme Activation
dc.subjectHindlimb
dc.subjectHumans
dc.subjectInduced Pluripotent Stem Cells
dc.subjectIschemia
dc.subjectMAP Kinase Signaling System
dc.subjectMesoderm
dc.subjectMice, Inbred NOD
dc.subjectMice, SCID
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectPerfusion
dc.subjectPyridines
dc.subjectPyrimidines
dc.typeArticle
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1186/s13287-018-1061-4
dc.description.sourcetitleStem cell research & therapy
dc.description.volume9
dc.description.issue1
dc.description.page313
dc.published.statePublished
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