title: Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin.
abstract: Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany Pediatric Hematology and Oncology, University Hospital Münster, Germany isabel.dorn@mpi-muenster.mpg.de holm.zaehres@mpi-muenster.mpg.de.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dorn
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany Institute for Transfusion Medicine and Transplantation Immunology, University Hospital Münster, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Klich
authors.affiliation: Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Arauzo-Bravo
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Radstaak
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Simeon
authors.initials: S
authors.lastname: Santourlidis
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Foued
authors.initials: F
authors.lastname: Ghanjati
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Teja F
authors.initials: TF
authors.lastname: Radke
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Olympia E
authors.initials: OE
authors.lastname: Psathaki
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany Institute for Neuropathology, University Hospital Münster, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.affiliation: Medical Department I, University of Lübeck, Germany LADR GmbH, Geesthacht, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kramer
authors.affiliation: LADR GmbH, Geesthacht, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Einhaus
authors.affiliation: UNIST, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Jeong Beom
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Kögler
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wernet
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany Faculty of Medicine, University of Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Institute for Transfusion Medicine and Transplantation Immunology, University Hospital Münster, Germany Clinics for Blood Group Serology and Transfusion Medicine, Medical University Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Schlenke
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Münster, Germany isabel.dorn@mpi-muenster.mpg.de holm.zaehres@mpi-muenster.mpg.de.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019175:DNA Methylation; D057890:Epigenomics; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger