title: Chemical conversion of human fibroblasts into functional Schwann cells.
abstract: Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific cells for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present a gene-free approach that allows efficient conversion of human fibroblasts via a transient progenitor stage into Schwann cells, the major glial cell type of peripheral nerves. Using a multikinase inhibitor, we transdifferentiated fibroblasts into transient neural precursors that were subsequently further differentiated into Schwann cells. The resulting induced Schwann cells (iSCs) expressed numerous Schwann cell-specific proteins and displayed neurosupportive and myelination capacity in vitro. Thus, we established a strategy to obtain mature Schwann cells from human postnatal fibroblasts under chemically defined conditions without the introduction of ectopic genes.
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland. Electronic address: eva_christina.thoma@roche.com.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Thoma
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Merkl
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Heckel
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Haab
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Knoflach
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Nowaczyk
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Flint
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Ravi
authors.initials: R
authors.lastname: Jagasia
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Sannah
authors.initials: S
authors.lastname: Jensen Zoffmann
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Hoa Hue
authors.initials: HH
authors.lastname: Truong
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Petitjean
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Graf
authors.affiliation: Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacone
mesh_terms: D000818:Animals; D002460:Cell Line; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries