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PMID: 19151700 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transgenic mice with defined combinations of drug-inducible reprogramming factors.

Nature biotechnology ·Vol. 27 ·No. 2 ·2009-02-00 ·Pages 169-71

Markoulaki S, Hanna J, Beard C, Carey BW, Cheng AW, Lengner CJ, Dausman JA, Fu D, Gao Q, Wu S, Cassady JP, Jaenisch R

Abstract

Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor was introduced. This approach creates a defined system for studying reprogramming mechanisms and allows screening of genetically homogeneous cells for compounds that can replace any transcription factor required for iPS cell derivation.

MeSH Terms
Animals Cell Differentiation/drug effects,genetics Cells, Cultured Chimera/genetics,metabolism Doxycycline/pharmacology Female Fibroblasts/metabolism Genetic Techniques Kruppel-Like Factor 4 Kruppel-Like Transcription Factors/genetics,metabolism Male Mice Mice, Transgenic Octamer Transcription Factor-3/genetics,metabolism Pluripotent Stem Cells Proto-Oncogene Proteins c-myc/genetics,metabolism Proviruses/genetics,metabolism SOXB1 Transcription Factors/genetics,metabolism Transcription Factors/drug effects,genetics
Chemicals
Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors Octamer Transcription Factor-3 Pou5f1 protein, mouse Proto-Oncogene Proteins c-myc SOXB1 Transcription Factors Sox2 protein, mouse Transcription Factors Doxycycline
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Markoulaki Styliani
The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Hanna Jacob
Beard Caroline
Carey Bryce W
Cheng Albert W
Lengner Christopher J
Dausman Jessica A
Fu Dongdong
Gao Qing
Wu Su
Cassady John P
Jaenisch Rudolf
References (12)
12 references, click to expand
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Article Info
Journal
Nature biotechnology
Abbr.
Nat Biotechnol
ISSN
1546-1696
DOI
10.1038/nbt.1520
Published
2009-02-00
Epub
2009-00-18
Pages
169-71
Language
English
Region
United States
NLM ID
9604648
PMCID
PMC2654270
Subset
IM
Grants
PHS HHS · 5-R01-HDO45022 · United States
NICHD NIH HHS · R01 HD045022-06 · United States
NCI NIH HHS · R37 CA084198-09 · United States
NCI NIH HHS · 5-R37-CA084198 · United States
NCI NIH HHS · 5-R01-CA087869 · United States
NCI NIH HHS · R37 CA084198 · United States
NICHD NIH HHS · R01 HD045022 · United States
NCI NIH HHS · R01 CA087869-08 · United States
NCI NIH HHS · R01 CA087869 · United States
External Links
PubMed source DOI: 10.1038/nbt.1520 PMC Full Text View journal details
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