The unfolded protein response regulator ATF6 promotes mesodermal differentiation

Kroeger, Heike; Grimsey, Neil; Paxman, Ryan J; Chiang, Wei‐Chieh; Plate, Lars; Jones, Ying; Shaw, Peter X.; Trejo, JoAnn; Tsang, Stephen H.; Powers, Evan T.; Kelly, Jeffery W.; Wiseman, R. Luke; Lin, Jonathan H.

doi:10.1126/scisignal.aan5785

Cited by 56 publications

(59 citation statements)

References 68 publications

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“…In humans, the two ATF6 genes are referred to as ATF6 (also known as ATF6α) and ATF6B (Haze et al, 2001). It has been recently found that hyper-activation of ATF6 in human embryonic stem cells (hESCs) not only promotes their expansion of the ER network, but also biases their differentiation into the mesodermal lineage (Kroeger et al, 2018). Conversely, loss-of-function mutations of ATF6 in induced pluripotent stem cells impede this mesodermal fate specification (Kroeger et al, 2018).…”

Section: The Role Of Atf6 In Animal Developmentmentioning

confidence: 99%

The unfolded protein response in metazoan development

Mitra

Ryoo

2019

Journal of Cell Science

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Eukaryotic cells respond to an overload of unfolded proteins in the endoplasmic reticulum (ER) by activating signaling pathways that are referred to as the unfolded protein response (UPR). Much UPR research has been conducted in cultured cells that exhibit no baseline UPR activity until they are challenged by ER stress initiated by chemicals or mutant proteins. At the same time, many genes that mediate UPR signaling are essential for the development of organisms ranging from Drosophila and fish to mice and humans, indicating that there is physiological ER stress that requires UPR in normally developing animal tissues. Recent studies have elucidated the tissue-specific roles of all three branches of UPR in distinct developing tissues of Drosophila, fish and mammals. As discussed in this Review, these studies not only reveal the physiological functions of the UPR pathways but also highlight a surprising degree of specificity associated with each UPR branch in development.

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Section: The Role Of Atf6 In Animal Developmentmentioning

confidence: 99%

The unfolded protein response in metazoan development

Mitra

Ryoo

2019

Journal of Cell Science

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“…Recently, a new role for ATF6a signaling in early stem cell differentiation was identified [113]. It was shown that the activation of ATF6a during stem cell differentiation resulted in the acceleration of differentiation events toward the mesodermal lineage generating functional endothelial cells that were able to undergo in vitro angiogenesis to form blood vessels; ATF6a additionally stimulated the loss of pluripotency [113]. In the same study, ATF6a was found to support the growth and maturation of the ER without activating a comprehensive ER stress responds.…”

Section: Discussionmentioning

confidence: 99%

ER stress and unfolded protein response in ocular health and disease

et al. 2018

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The human eye is the organ that is able to react to light in order to provide sharp three-dimensional and colored images. Unfortunately, the health of the eye can be impacted by various stimuli that can lead to vision loss, such as environmental changes, genetic mutations, or aging. Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling have been detected in many diverse ocular diseases, and chemical and genetic approaches to modulate ER stress and specific UPR regulatory molecules have shown beneficial effects in animal models of eye disease. This review highlights specific eye diseases associated with ER stress and UPR activity, based on a recent symposia exploring this theme.

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“…ERS (Kroeger et al, 2018) GSE106847 RNA-seq ATF6 encodes a transcription factor that is activated during the Unfolded Protein Response to protect cells from ER stress. Comparison was made between ATF6-activated and control cells.…”

Section: Datasets Name (Acronym) Access To Data Technologymentioning

confidence: 99%

DOMINO: a novel algorithm for network-based identification of active modules with reduced rate of false calls

Levi

Elkon

Shamir

2020

Preprint

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Network-based module discovery (NBMD) methods are central to analysis of omics data. Such algorithms receive a gene network and nodes' activity scores as input and report sub-networks (modules) that are putatively biologically active. Although such methods exist for almost two decades, only a handful of studies attempted to compare the biological signals captured by different methods. Here, we systematically evaluated six popular NBMD methods on gene expression (GE) and GWAS data . Notably, we observed that GO terms enriched in modules detected by these methods on the real data were often also enriched after randomly permuting the input data. To tackle this bias, we designed a method that evaluates the empirical significance of GO terms reported as enriched in modules. We used the method to fashion five novel performance criteria for evlautating NBMD methods. Last, we developed a novel NBMD algorithm called DOMINO. In extensive testing on GE and GWAS data it outperformed the other six algorithms. Software is available at https://github.com/Shamir-Lab/.

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The unfolded protein response regulator ATF6 promotes mesodermal differentiation

Cited by 56 publications

References 68 publications

The unfolded protein response in metazoan development

The unfolded protein response in metazoan development

ER stress and unfolded protein response in ocular health and disease

DOMINO: a novel algorithm for network-based identification of active modules with reduced rate of false calls

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