Ell3 functions as a critical decision maker at the crossroad between stem cell senescence and apoptosis
Jae-Yong Lee1, Soo-Hong Lee1, Kwang-Soo Kim1
1Department of Biomedical Science, College of Life Science and CHA Stem Cell Institute, CHA University, 335, Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Korea.
Background:
Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the regulation of senescence and apoptosis of stem cells.
Methods:
We analyzed the senescence of Ell3-suppressed stem cells by mitochondrial activity, β-gal (+) cells, and lineage differentiation efficiency. The apoptosis of Ell3-overexpressing stem cells was analyzed by Annexin V staining, Immunoblot, and Live&dead assay. In addition, chromatin immunoprecipitation and luciferase assays were used to demonstrate p53 functions as a direct transcriptional activator of Ell3.
Results:
Suppression of Ell3 expression induced senescence in stem cells by increasing Bcl-2 expression. Unlike the effect of Ell3 suppression, the ectopic expression of Ell3 induces apoptosis of stem cells and induces apoptosis of adjacent cells. In addition, p53 functions as a direct transcriptional activator of Ell3 during the stem cell apoptosis.
Conclusions:
We suggest that the function of Ell3 is associated with the p53-Bcl2 axis in both senescent and apoptotic ADSCs.
Insights
Ell3 (elongation factor) regulates stem cell senescence and apoptosis. Its suppression induces senescence via Bcl-2, while overexpression triggers apoptosis, both linked to the p53-Bcl2 axis.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Cellular Senescence
Background:
- Ell3 is an RNA polymerase II elongation factor with known roles in stem cell differentiation and cancer therapy.
- Limited research exists on Ell3's involvement in stem cell senescence and apoptosis.
Purpose of the Study:
- To investigate the role of Ell3 in regulating stem cell senescence and apoptosis.
- To elucidate the molecular mechanisms underlying Ell3's function in these processes.
Main Methods:
- Analysis of stem cell senescence markers (mitochondrial activity, β-gal staining, differentiation efficiency) upon Ell3 suppression.
- Assessment of stem cell apoptosis using Annexin V staining, immunoblotting, and Live&dead assays for Ell3 overexpression.
- Chromatin immunoprecipitation and luciferase assays to determine the transcriptional regulation of Ell3 by p53.
Main Results:
- Ell3 suppression induced stem cell senescence, correlated with increased Bcl-2 expression.
- Ectopic expression of Ell3 promoted stem cell apoptosis and induced apoptosis in adjacent cells.
- p53 was identified as a direct transcriptional activator of Ell3.
Conclusions:
- Ell3 plays a critical role in regulating stem cell senescence and apoptosis.
- The function of Ell3 in senescent and apoptotic adipose-derived stem cells (ADSCs) is linked to the p53-Bcl2 signaling axis.
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