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Status |
Public on Feb 13, 2017 |
Title |
Retinoic acid specifically enhances embryonic stem cell metastate marked by Zscan4 |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation.
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Overall design |
emeral+/-, retinoic acid cell sorting
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Contributor(s) |
Falco G, Ko M |
Citation(s) |
26840068 |
Submission date |
Dec 14, 2015 |
Last update date |
Feb 13, 2017 |
Contact name |
Minoru S.H. Ko |
E-mail(s) |
kom@mail.nih.gov
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Phone |
410-558-8359
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Organization name |
NIH
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Department |
National Institute on Aging
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Lab |
Lab of Genetics
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Street address |
251 Bayview Blvd, Suite 100, 10C
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City |
Baltimore |
State/province |
MD |
ZIP/Postal code |
21224 |
Country |
USA |
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Platforms (1) |
GPL4358 |
NIA Mouse 44K Microarray v2.2 (Whole Genome 60-mer Oligo) |
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Samples (8)
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Relations |
BioProject |
PRJNA305888 |
Supplementary file |
Size |
Download |
File type/resource |
GSE75977_RAW.tar |
79.8 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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