Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression (original) (raw)

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,

Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine

, Boston, Massachusetts,

USA

Harvard Stem Cell Institute, Free University of Berlin

, Berlin,

Germany

Department of Biology, Chemistry, and Pharmacy, Free University of Berlin

, Berlin,

Germany

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Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine

, Boston, Massachusetts,

USA

Harvard Stem Cell Institute, Free University of Berlin

, Berlin,

Germany

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,

Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine

, Boston, Massachusetts,

USA

Harvard Stem Cell Institute, Free University of Berlin

, Berlin,

Germany

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,

Whitehead Institute and Department of Biology, Massachusetts Institute of Technology

, Cambridge, Massachusetts,

USA

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Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine

, Boston, Massachusetts,

USA

Harvard Stem Cell Institute, Free University of Berlin

, Berlin,

Germany

Correspondence: Konrad Hochedlinger, Ph.D., Massachusetts General Hospital, 185 Cambridge Street, CPZN 4242, Boston, Massachusetts 02114, USA. Telephone: 617-643-2075; Fax: 617-643-3170; e-mail: khochedlinger@helix.mgh.harvard.edu

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Sarah Eminli, Jochen Utikal, Katrin Arnold, Rudolf Jaenisch, Konrad Hochedlinger, Reprogramming of Neural Progenitor Cells into Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 Expression, Stem Cells, Volume 26, Issue 10, October 2008, Pages 2467–2474, https://doi.org/10.1634/stemcells.2008-0317
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Abstract

Expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and β cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are equally amenable to reprogramming into iPS cells by the same combination of factors. To test this, we have isolated genetically marked neural progenitor cells (NPCs) from neonatal mouse brains and infected them with viral vectors expressing Oct4, Sox2, Klf4, and c-Myc. Infected NPCs gave rise to iPS cells that expressed markers of embryonic stem cells, showed demethylation of pluripotency genes, formed teratomas, and contributed to viable chimeras. In contrast to other somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did not require viral Sox2 expression for reprogramming into iPS cells. Our data show that in addition to mesoderm- and endoderm-derived cell types, neural progenitor cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting that in vitro reprogramming is a universal process. These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context.

Disclosure of potential conflicts of interest is found at the end of this article.

Copyright © 2008 AlphaMed Press

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model)

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