2. Academic Validation
  3. Transient activation of the UPRER is an essential step in the acquisition of pluripotency during reprogramming

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

  • Sci Adv. 2019 Apr 10;5(4):eaaw0025. doi: 10.1126/sciadv.aaw0025.
Milos S Simic 1 2 3,  Erica A Moehle 1 2 3,  Robert T Schinzel 1 2 3,  Franziska K Lorbeer 3,  Jonathan J Halloran 1 2 3,  Kartoosh Heydari 3,  Melissa Sanchez 1 2 3,  Damien Jullié 4,  Dirk Hockemeyer 3,  Andrew Dillin 1 2 3
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 2 California Institute for Regenerative Medicine, Berkeley, CA 94720, USA.
  • 3 University of California, Berkeley, Berkeley, CA 94720, USA.
  • 4 University of California, San Francisco, San Francisco, CA 94143, USA.
PMID: 30989118 DOI: 10.1126/sciadv.aaw0025
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 (UPRER), the mitochondrial UPR, and the heat shock response, which ensure proteome quality during stress, are activated during reprogramming. The UPRER is particularly crucial, and its ectopic, transient activation, genetically or pharmacologically, enhances reprogramming. Last, stochastic activation of the UPRER 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 UPRER to remodel the ER and its proteome.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-17537
    99.90%, IRE1 Inhibitor