TY - JOUR
T1 - Effects of oxidative and thermal stresses on stress granule formation in human induced pluripotent stem cells
AU - Palangi, Freshteh
AU - Samuel, Samson M.
AU - Thompson, I. Richard
AU - Triggle, Chris R.
AU - Emara, Mohamed M.
N1 - Publisher Copyright:
© 2017 Palangi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/7/26
Y1 - 2017/7/26
N2 - 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 eIF2a 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.
AB - 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 eIF2a 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.
KW - Messenger-rna translation
KW - Processing bodies
KW - Gene-expression
KW - P-bodies
KW - Eif2-alpha phosphorylation
KW - Saccharomyces-cerevisiae
KW - Protein-synthesis
KW - Self-renewal
KW - Heat-shock
KW - Binding
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=hbku_researchportal&SrcAuth=WosAPI&KeyUT=WOS:000406371800076&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1371/journal.pone.0182059
DO - 10.1371/journal.pone.0182059
M3 - Article
C2 - 28746394
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e0182059
ER -