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The Unfolded Protein Response Regulator, ATF6, Promotes Mesodermal Differentiation

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106847 | GEO | 2017/11/14

SECONDARY ACCESSION(S): PRJNA418171

REPOSITORIES: GEO

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ATF6 is required for the survival of castration-resistant prostate cancer cells

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The Unfolded Protein Response Regulator, ATF6, Promotes Mesodermal Differentiation

Project description:The Unfolded Protein Response Regulator, ATF6, Promotes Mesodermal Differentiation

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