Transgenic mice with defined combinations of drug-inducible reprogramming factors.
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.
Markoulaki
Styliani
S
The Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Hanna
Jacob
J
Beard
Caroline
C
Carey
Bryce W
BW
Cheng
Albert W
AW
Lengner
Christopher J
CJ
Dausman
Jessica A
JA
Fu
Dongdong
D
Gao
Qing
Q
Wu
Su
S
Cassady
John P
JP
Jaenisch
Rudolf
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005821:Genetic Techniques; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*
C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; D004318:Doxycycline