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| Status |
Public on Jan 25, 2017 |
| Title |
Genetic Redundancy of GATA Factors in Extraembryonic Trophoblast Lineage Ensures Progression of both Pre and Postimplantation Mammalian Development [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
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| Overall design |
Gata2f/f;Gata3f/f;UBC-cre/ERT2 mTS cells were cultured in presence or absence of 4-hydroxytamoxifen (4-OHT) in MEF conditioned media FGF4 and heparin. Deletion of respective genes were confirmed by PCR using genomic DNA from individual samples. Whole cell-lysates were used to prepare RNA using Qiagen RNeasy Mini Kit with on column DNase digestion. RNA-seq analysis were performed using a illumina HiSeq2000 platform.
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| Contributor(s) |
Soumen P, Pratik H, Sumedha G |
| Citation(s) |
28232602 |
| |
| Submission date |
Dec 12, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Sumedha S Gunewardena |
| Phone |
9139456878
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| Organization name |
University of kansas medical center
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| Department |
Dept. of Molecular and Integrative Physiology
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| Street address |
2146 West 39th Avenue
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| City |
Kansas City |
| State/province |
Kansas |
| ZIP/Postal code |
66160 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE92295 |
Genetic Redundancy of GATA Factors in Extraembryonic Trophoblast Lineage Ensures Progression of both Pre and Postimplantation Mammalian Development |
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| Relations |
| BioProject |
PRJNA357115 |
| SRA |
SRP094978 |
