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Series GSE69356 Query DataSets for GSE69356
Status Public on Jul 01, 2015
Title Dazl is required for TET-mediated reprogramming to a naïve pluripotent state (II)
Organism Mus musculus
Experiment type Expression profiling by array
Summary Embryonic stem cell (ESC) cultures display a heterogeneous gene expression profile, ranging from a pristine naïve pluripotent state to a primed epiblast state. While it is known that the addition of inhibitors of GSK3β and MEK (so-called 2i conditions) push ESC cultures towards a more homogeneous naïve pluripotent state, the molecular underpinnings of this naïve transition are not completely understood. Here we demonstrate that Dazl, a RNA-binding protein previously thought to be expressed specifically in developing primordial germ cells (PGCs), marks a subpopulation of ESCs in vitro that is actively transitioning toward naïve pluripotency. In the absence of Dazl expression, ESCs fail to induce proper expression of Tet enzymes required for 5-hydroxymethylation in 2i-culture conditions. As a result, 5-hydroxymethylation of methylated cystosine residues is impaired. Indeed, we demonstrate that Tet1 and Tet2 are mRNA targets of Dazl, indicating that Dazl might play a role in protection or stabilizing these mRNA molecules. Our results provide insight in the regulation of the acquisition of naïve pluripotency and demonstrate that Dazl is required for TET-mediated cytosine hydroxymethylation in cells that are actively reprogramming to a pluripotent ground state.
 
Overall design RNA-IP experiments were used to identify the RNA species bound to DAZL.
 
Contributor(s) Welling M, Chen H, Munoz J, Kester L, Junker JP, Mischerikov N, Kuijk E, Silberstein L, Kharchenko PV, Geens M, van de Velde H, van Oudenaarden A, Heck AJ, Geijsen N
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Submission date May 29, 2015
Last update date May 10, 2018
Contact name Niels Geijsen
E-mail(s) n.geijsen@hubrecht.eu
Organization name Hubrecht Institute
Street address Uppsalalaan 8
City Utrecht
ZIP/Postal code 3584 CT
Country Netherlands
 
Platforms (1)
GPL4134 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version)
Samples (8)
GSM1698511 ES2i_Input_1
GSM1698512 ES2i_Input_2
GSM1698513 ES2i_Input_3
This SubSeries is part of SuperSeries:
GSE69357 Dazl is required for TET-mediated reprogramming to a naïve pluripotent state
Relations
BioProject PRJNA285292

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE69356_ES2i_RIP_GeneSifterExport.txt.gz 2.3 Mb (ftp)(http) TXT
GSE69356_RAW.tar 55.1 Mb (http)(custom) TAR (of TXT)
Processed data are available on Series record
Processed data included within Sample table

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