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Transient activation of the UPR^ER is an essential step in the acquisition of pluripotency during reprogramming.

ABSTRACT: Somatic cells can be reprogrammed into pluripotent stem cells using the Yamanaka transcription factors. Reprogramming requires both epigenetic landscape reshaping and global remodeling of cell identity, structure, basic metabolic processes, and organelle form and function. We hypothesize that variable regulation of the proteostasis network and its influence upon the protein-folding environment within cells and their organelles is responsible for the low efficiency and stochasticity of reprogramming. We find that the unfolded protein response of the endoplasmic reticulum (UPR^ER), the mitochondrial UPR, and the heat shock response, which ensure proteome quality during stress, are activated during reprogramming. The UPR^ER is particularly crucial, and its ectopic, transient activation, genetically or pharmacologically, enhances reprogramming. Last, stochastic activation of the UPR^ER predicts reprogramming efficiency in naïve cells. Thus, the low efficiency and stochasticity of cellular reprogramming are due partly to the inability to properly initiate the UPR^ER to remodel the ER and its proteome.

SUBMITTER: Simic MS

PROVIDER: S-EPMC6457941 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Transient activation of the UPR<sup>ER</sup> is an essential step in the acquisition of pluripotency during reprogramming.

Simic Milos S MS Moehle Erica A EA Schinzel Robert T RT Lorbeer Franziska K FK Halloran Jonathan J JJ Heydari Kartoosh K Sanchez Melissa M Jullié Damien D Hockemeyer Dirk D Dillin Andrew A

Science advances 20190410 4

Somatic cells can be reprogrammed into pluripotent stem cells using the Yamanaka transcription factors. Reprogramming requires both epigenetic landscape reshaping and global remodeling of cell identity, structure, basic metabolic processes, and organelle form and function. We hypothesize that variable regulation of the proteostasis network and its influence upon the protein-folding environment within cells and their organelles is responsible for the low efficiency and stochasticity of reprogramm ...[more]

PMID: 30989118

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Project description:In plants, multiple detached tissues are capable of forming a pluripotent cell mass, termed callus, when cultured on media containing appropriate plant hormones. Recent studies demonstrated that callus resembles the root-tip meristem, even if it is derived from aerial organs. This finding improves our understanding of the regeneration process of plant cells; however, the molecular mechanism that guides cells of different tissue types to form a callus still remains elusive. Here, we show that genome-wide reprogramming of histone H3 lysine 27 trimethylation (H3K27me3) is a critical step in the leaf-to-callus transition. The Polycomb Repressive Complex 2 (PRC2) is known to function in establishing H3K27me3. By analyzing callus formation of mutants corresponding to different histone modification pathways, we found that leaf blades and/or cotyledons of the PRC2 mutants curly leaf swinger (clf swn) and embryonic flower2 (emf2) were defective in callus formation. We identified the H3K27me3-covered loci in leaves and calli by a ChIP-chip assay, and we found that in the callus H3K27me3 levels decreased first at certain auxin-pathway genes. The levels were then increased at specific leaf genes but decreased at a number of root-regulatory genes. Changes in H3K27me3 levels were negatively correlated with expression levels of the corresponding genes. One possible role of PRC2-mediated H3K27me3 in the leaf-to-callus transition might relate to elimination of leaf features by silencing leaf-regulatory genes, as most leaf-preferentially expressed regulatory genes could not be silenced in the leaf explants of clf swn. In contrast to the leaf explants, the root explants of both clf swn and emf2 formed calli normally, possibly because the root-to-callus transition bypasses the leaf gene silencing process. Furthermore, our data show that PRC2-mediated H3K27me3 and H3K27 demethylation act in parallel in the reprogramming of H3K27me3 during the leaf-to-callus transition, suggesting a general mechanism for cell fate transition in plants.

Dataset Information

Transient activation of the UPR^ER is an essential step in the acquisition of pluripotency during reprogramming.

Publications

Transient activation of the UPR<sup>ER</sup> is an essential step in the acquisition of pluripotency during reprogramming.

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Dataset Information

Transient activation of the UPRER is an essential step in the acquisition of pluripotency during reprogramming.

Publications

Transient activation of the UPR<sup>ER</sup> is an essential step in the acquisition of pluripotency during reprogramming.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Transient activation of the UPR^ER is an essential step in the acquisition of pluripotency during reprogramming.