title: Cell type of origin influences iPSC generation and differentiation to cells of the hematoendothelial lineage.
abstract: The use of induced pluripotent stem cells (iPSCs) as a source of cells for cell-based therapy in regenerative medicine is hampered by the limited efficiency and safety of the reprogramming procedure and the low efficiency of iPSC differentiation to specialized cell types. Evidence suggests that iPSCs retain an epigenetic memory of their parental cells with a possible influence on their differentiation capacity in vitro. We reprogramme three cell types, namely human umbilical cord vein endothelial cells (HUVECs), endothelial progenitor cells (EPCs) and human dermal fibroblasts (HDFs), to iPSCs and compare their hematoendothelial differentiation capacity. HUVECs and EPCs were at least two-fold more efficient in iPSC reprogramming than HDFs. Both HUVEC- and EPC-derived iPSCs exhibited high potentiality toward endothelial cell differentiation compared with HDF-derived iPSCs. However, only HUVEC-derived iPSCs showed efficient differentiation to hematopoietic stem/progenitor cells. Examination of DNA methylation at promoters of hematopoietic and endothelial genes revealed evidence for the existence of epigenetic memory at the endothelial genes but not the hematopoietic genes in iPSCs derived from HUVECs and EPCs indicating that epigenetic memory involves an endothelial differentiation bias. Our findings suggest that endothelial cells and EPCs are better sources for iPSC derivation regarding their reprogramming efficiency and that the somatic cell type used for iPSC generation toward specific cell lineage differentiation is of importance.
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon 4 Road, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand.
authors.forename: Jitrada
authors.initials: J
authors.lastname: Phetfong
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon 4 Road, Salaya, Phuttamonthon, Nakhon Pathom, 73170, Thailand. aungkura.jer@mahidol.ac.th.
authors.forename: Aungkura
authors.initials: A
authors.lastname: Supokawej
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Methichit
authors.initials: M
authors.lastname: Wattanapanitch
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Division of Cell Biology, Department of Pre-clinical Sciences, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.|Center of Excellence in Stem Cell Research, Thammasat University, Pathum Thani, Thailand.
authors.forename: Pakpoom
authors.initials: P
authors.lastname: Kheolamai
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.|Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok-noi, Bangkok, 10700, Thailand.
authors.forename: Yaowalak
authors.initials: Y
authors.lastname: U-Pratya
authors.affiliation: Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. surapolsi@gmail.com.|Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Bangkok-noi, Bangkok, 10700, Thailand. surapolsi@gmail.com.
authors.forename: Surapol
authors.initials: S
authors.lastname: Issaragrisil
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002469:Cell Separation; D065150:Cellular Reprogramming; D019175:DNA Methylation / Q000235:genetics; D020405:Dermis / Q000166:cytology; D066026:Endothelial Progenitor Cells / Q000166:cytology; D005347:Fibroblasts; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D011401:Promoter Regions, Genetic / Q000235:genetics
keywords: Endothelial differentiation; Epigenetic memory; HUVECs; Hematopoietic differentiation; Induced pluripotent stem cells