Origin-Dependent Neural Cell Identities in Differentiated Human iPSCs In Vitro and after Transplantation into the Mouse Brain
Gunnar Hargus,
Marc Ehrlich,
Marcos J. Araúzo-Bravo,
Kathrin Hemmer,
Anna-Lena Hallmann,
Peter Reinhardt,
Kee-Pyo Kim,
Kenjiro Adachi,
Simeon Santourlidis,
Foued Ghanjati,
Mareike Fauser,
Christiana Ossig,
Alexander Storch,
Jeong Beom Kim,
Jens C. Schwamborn,
Jared Sterneckert,
Hans R. Schöler,
Tanja Kuhlmann,
Holm Zaehres
Affiliations
Gunnar Hargus
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Marc Ehrlich
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Marcos J. Araúzo-Bravo
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Kathrin Hemmer
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Anna-Lena Hallmann
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Peter Reinhardt
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Kee-Pyo Kim
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Kenjiro Adachi
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Simeon Santourlidis
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Foued Ghanjati
Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Mareike Fauser
Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany
Christiana Ossig
Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany
Alexander Storch
Division of Neurodegenerative Diseases, Department of Neurology and Center for Regenerative Therapies Dresden (CRTD), University of Technology, 01307 Dresden, Germany
Jeong Beom Kim
UNIST, Ulsan National Institute of Science and Technology, Ulsan 689-798, South Korea
Jens C. Schwamborn
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362 Esch-sur-Alzette, Luxembourg
Jared Sterneckert
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Hans R. Schöler
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
Tanja Kuhlmann
Institute of Neuropathology, University Hospital Münster, 48149 Münster, Germany
Holm Zaehres
Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
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.
