The Role of Stress Granules in the Neuronal Differentiation of Stem Cells

• Published in: Molecules and cells Vol. 43; no. 10; pp. 848 - 855
• Main Authors: Jeong, Sin-Gu, Ohn, Takbum, Jang, Chul Ho, Vijayakumar, Karthikeyan, Cho, Gwang-Won
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 31.10.2020; 한국분자세포생물학회
• Subjects: Cell Differentiation - drug effects; Cell Survival; Cells, Cultured; Cinnamates - pharmacology; Cytoplasmic Granules - drug effects; Cytoplasmic Granules - metabolism; DNA Helicases - metabolism; Eukaryotic Initiation Factor-2 - metabolism; Gene Expression Regulation; Humans; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Neurofilament Proteins - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Phosphorylation - drug effects; Poly-ADP-Ribose Binding Proteins - metabolism; Protein Biosynthesis - drug effects; RNA Helicases - metabolism; RNA Recognition Motif Proteins - metabolism; T-Cell Intracellular Antigen-1 - metabolism; Thiourea - analogs & derivatives; Thiourea - pharmacology; 생물학; stem cells; eukaryotic translation initiation factor 2 alpha; mesenchymal stem cells; stress granule; gene expression; neuronal differentiation
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2020.0135

creativecommons.org/licenses/by-nc-sa/3.0/. Cells assemble stress granules (SGs) to protect their RNAs from exposure to harmful chemical reactions induced by environmental stress. These SGs release RNAs, which resume translation once the stress is relieved. During stem cell differentiation, gene expression is altered to allow cells to adopt various functional and morphological features necessary to differentiate. This process induces stress within a cell, and cells that cannot overcome this stress die. Here, we investigated the role of SGs in the progression of stem cell differentiation. SGs aggregated during the neuronal differentiation of human bone marrow-mesenchymal stem cells, and not in cell lines that could not undergo differentiation. SGs were observed between one and three hours post-induction; RNA translation was restrained at the same time. Immediately after disassembly of SGs, the expression of the neuronal marker neurofilament-M (NFM) gradually increased. Assembled SGs that persisted in cells were exposed to salubrinal, which inhibited the dephosphorylation of eukaryotic translation initiation factor 2 subunit 1 (eIF2α), and in eIF2α/S51D mutant cells. When eIF2α/S51A mutant cells differentiated, SGs were not assembled. In all experiments, the disruption of SGs was accompanied by delayed NF-M expression and the number of neuronally differentiated cells was decreased. Decreased differentiation was accompanied by decreased cell viability, indicating the necessity of SGs for preventing cell death during neuronal differentiation. Collectively, these results demonstrate the essential role of SGs during the neuronal differentiation of stem cells.