Distinct enhancer activity of Oct4 in naive and primed mouse pluripotency

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Title
Distinct enhancer activity of Oct4 in naive and primed mouse pluripotency
Author(s)
H W Choi; J Y Joo; Y J Hong; J S Kim; H Song; Jeong Woong Lee; G Wu; H R Scholer; J T Do
Bibliographic Citation
Stem Cell Reports, vol. 7, no. 5, pp. 911-926
Publication Year
2016
Abstract
Naive and primed pluripotent stem cells (PSCs) and germ cells express the Oct4 gene. The Oct4 gene contains two cis-regulatory elements, the distal enhancer (DE) and proximal enhancer (PE), which differentially control Oct4 expression in a cell-type-specific and stage-specific manner. Here, we generated double transgenic mice carrying both Oct4-ΔPE-GFP and Oct4-ΔDE-tdTomato (RFP), enabling us to simultaneously monitor the activity of DE and PE. Oct4 expression is stage-specifically regulated by DE and PE during embryonic and germ cell development. Using this dual reporter system, we successfully cultured pure populations of naive (GFP+RFP?) and primed (GFP?RFP+) PSCs. We found that GFP+RFP? cells were metastable (not naive) in serum-containing medium; stable naive pluripotent cells were observed in medium containing two inhibitors (Meki and GSKi) but lacked serum. Finally, we suggest that the activity of Oct4 DE and PE is regulated by the repressive histone marks and DNA methylation in a cell-type-specific manner
Keyword
enhancernaive pluripotencyOct4primed pluripotency
ISSN
2213-6711
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.stemcr.2016.09.012
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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