Engineered zinc finger proteins for controlling stem cell fate.
Stem cells are functionally defined as progenitor cells that can self-renew and differentiate. Critical transitions in these cells are controlled via signaling pathways and subsequent transcriptional regulation. Technologies capable of modulating the levels of gene expression, especially those of transcription factors, represent powerful tools for research and could potentially be used in therapeutic applications. In this study, we evaluated the ability of synthetic zinc finger protein transcription factors (ZFP-TFs) to cause the differentiation of embryonic stem (ES) cells. We constructed ZFP-TFs that target the mouse Oct-4 gene (which is a major regulator of ES cell pluripotency and self-renewal). These designed transcription factors were able to regulate the transcription of Oct-4, affecting the expression of downstream genes and thus regulating ES cell differentiation.
Bartsevich
Victor V
VV
Sangamo BioSciences, Inc., Point Richmond Tech Center, Richmond, California 94804, USA. victorb@sangamo.com
Miller
Jeffrey C
JC
Case
Casey C
CC
Pabo
Carl O
CO
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D051379:Mice; D050814:Octamer Transcription Factor-3; D015202:Protein Engineering / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014157:Transcription Factors