title: Origin-dependent neural cell identities in differentiated human iPSCs in vitro and after transplantation into the mouse brain.
abstract: The differentiation capability of induced pluripotent stem cells (iPSCs) toward certain cell types for disease modeling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from fetal neural stem cells (fNSCs), dermal fibroblasts, or cord blood CD34(+) hematopoietic progenitor cells. Neural progenitor cells (NPCs) and neurons could be generated at similar efficiencies from all iPSCs. Transcriptomics analysis of the whole genome and of neural genes revealed a separation of neuroectoderm-derived iPSC-NPCs from mesoderm-derived iPSC-NPCs. Furthermore, we found genes that were similarly expressed in fNSCs and neuroectoderm, but not in mesoderm-derived iPSC-NPCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival of neuroectoderm-derived cells in vivo. These results indicate distinct origin-dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hargus
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Ehrlich
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, 20014 San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hemmer
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Hallmann
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhardt
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Kee-Pyo
authors.initials: KP
authors.lastname: Kim
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Simeon
authors.initials: S
authors.lastname: Santourlidis
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Foued
authors.initials: F
authors.lastname: Ghanjati
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Fauser
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany.
authors.forename: Christiana
authors.initials: C
authors.lastname: Ossig
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
authors.affiliation: UNIST, Ulsan National Institute of Science and Technology, Ulsan 689-798, South Korea.
authors.forename: Jeong Beom
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg; Stem Cell Biology and Regeneration Group, Institute of Cell Biology, ZMBE, Westfälische Wilhelms-University Münster, 48149 Münster, Germany.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Schwamborn
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Jared
authors.initials: J
authors.lastname: Sterneckert
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany; Faculty of Medicine, University of Münster, 48149 Münster, Germany. Electronic address: office@mpi-muenster.mpg.de.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D054258:Neural Plate / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; D049452:Green Fluorescent Proteins