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Chemical conversion of human fibroblasts into functional schwann cells


Thoma, Eva C; Merkl, Claudia; Heckel, Tobias; Haab, Rachel; Knoflach, Frederic; Nowaczyk, Corinne; Flint, Nicholas; Jagasia, Ravi; Jensen Zoffmann, Sannah; Truong, Hoa Hue; Petitjean, Pascal; Jessberger, Sebastian; Graf, Martin; Iacone, Roberto (2014). Chemical conversion of human fibroblasts into functional schwann cells. Stem Cell Reports, 3(4):539-547.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:14 October 2014
Deposited On:27 Feb 2015 09:36
Last Modified:05 Apr 2016 18:32
Publisher:Cell Press (Elsevier)
ISSN:2213-6711
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.stemcr.2014.07.014
PubMed ID:25358782
Permanent URL: https://doi.org/10.5167/uzh-101186

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