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| Status |
Public on Nov 14, 2017 |
| Title |
The Unfolded Protein Response Regulator, ATF6, Promotes Mesodermal Differentiation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
ATF6 encodes a transcription factor that is activated during the Unfolded Protein Response to protect cells from ER stress. Loss of ATF6α and its paralog ATF6β, results in embryonic lethality, notochord dysgenesis, and in people, loss of ATF6α specifically, results in malformed neuroretina and congenital vision loss. These phenotypes implicate an essential role for ATF6 during vertebrate development. We investigated the function of ATF6 in development using human stem cells undergoing differentiation into multipotent germ layers, nascent tissues, and organs. We artificially activated ATF6 in stem cells with a recently identified small molecule ATF6 agonist, and we inhibited ATF6 using iPSCs from patients harboring ATF6 mutations. We discovered that ATF6 suppresses pluripotency, enhances differentiation, and surprisingly, guides stem cells toward mesodermal cell fates. Our findings reveal a novel role for ATF6 during differentiation and identify a new strategy to robustly create mesodermal tissues through modulation of the ATF6 arm of the UPR.
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| Overall design |
Comparison of the transcriptomes of pluripotent stem cells before treatment and 13 days after treatment with either AA147 (a small molecule that activates the ATF6 pathway of the UPR) or RP22 (an inactive analog of AA147)
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| |
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| Contributor(s) |
Kroeger H, Powers ET, Wiseman RL, Lin JH |
| Citation(s) |
29440509 |
| |
| Submission date |
Nov 13, 2017 |
| Last update date |
May 21, 2019 |
| Contact name |
Evan Thomas Powers |
| E-mail(s) |
epowers@scripps.edu
|
| Organization name |
The Scripps Research Institute
|
| Department |
Chemistry
|
| Street address |
10550 North Torrey Pines Rd
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA418171 |
| SRA |
SRP124873 |
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