Abstract
Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated. Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H2O2), induce SG formation in human induced (hi) PSCs. Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress. Moreover, we showed that SA and HS, but not H2O2, promote eIF2α phosphorylation in hiPSCs forming SGs. Analysis of pluripotent protein expression showed that HS significantly reduced all tested markers (OCT4, SOX2, NANOG, KLF4, L1TD1, and LIN28A), while SA selectively reduced the expression levels of NANOG and L1TD1. Finally, in addition to LIN28A and L1TD1, we identified DPPA5 (pluripotent protein marker) as a novel component of SGs. Collectively, these results provide new insights into the molecular cues of hiPSCs responses to environmental insults.
Highlights
Environmental stress induces swift response within the cell that leads to a timely adaptation of different regulatory processes such as chromatin remodeling, transcriptional regulation, and translational control that maximize the ability of cells to survive under these stressful conditions [1]
We found that hiPSCs are able to induce stress granules (SGs) formation depending on the insult used
DPPA5, but not non-RNA binding pluripotent proteins (SOX2, KLF4, and NANOG), are selectively recruited to SGs in stressed hiPSCs, and (iv) DPPA5 is a novel component of SGs
Summary
Environmental stress induces swift response within the cell that leads to a timely adaptation of different regulatory processes such as chromatin remodeling, transcriptional regulation, and translational control that maximize the ability of cells to survive under these stressful conditions [1]. Cessation of cell protein synthesis is caused by translation initiation inhibition that leads to rapid polysome disassembly and is associated with the activation of regulatory stress-response programs. A consequence of such translation inhibition regulatory mechanism is the assembly of cytoplasmic nonmembranous structures known as stress granules (SGs)
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