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PMID: 21521790 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Direct reprogramming of mouse fibroblasts to neural progenitors.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 108 ·No. 19 ·2011-05-10 ·Pages 7838-43

Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S

Abstract

The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor-based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.

MeSH Terms
Animals Cell Lineage Cell Proliferation Cell Transdifferentiation Culture Media Cytological Techniques Fibroblasts/cytology,metabolism Gene Expression Induced Pluripotent Stem Cells/cytology,metabolism Kruppel-Like Factor 4 Kruppel-Like Transcription Factors/biosynthesis Mice Models, Biological Neural Stem Cells/cytology,metabolism Octamer Transcription Factor-3/biosynthesis,genetics Promoter Regions, Genetic Proto-Oncogene Proteins c-myc/biosynthesis SOXB1 Transcription Factors/biosynthesis,genetics,metabolism
Chemicals
Culture Media Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Myc protein, mouse Octamer Transcription Factor-3 Pou5f1 protein, mouse Proto-Oncogene Proteins c-myc SOXB1 Transcription Factors Sox1 protein, mouse Sox2 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kim Janghwan
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Efe Jem A
Zhu Saiyong
Talantova Maria
Yuan Xu
Wang Shufen
Lipton Stuart A
Zhang Kang
Ding Sheng
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1103113108
Published
2011-05-10
Epub
2011-00-26
Pages
7838-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3093517
Subset
IM
Grants
NEI NIH HHS · R01 EY021374 · United States
NEI NIH HHS · R01EY021374 · United States
NIEHS NIH HHS · P01ES016738 · United States
NEI NIH HHS · R01 EY005477 · United States
NINDS NIH HHS · P30 NS057096 · United States
NEI NIH HHS · R01 EY05477 · United States
NICHD NIH HHS · P01 HD029587 · United States
NIEHS NIH HHS · P01 ES016738 · United States
NEI NIH HHS · R01 EY018660 · United States
NICHD NIH HHS · P01 HD29587 · United States
External Links
PubMed source DOI: 10.1073/pnas.1103113108 PMC Full Text View journal details
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