Ell3 functions as a critical decision maker at the crossroad between stem cell senescence and apoptosis

Stem Cell Res Ther. 2019 Jan 17;10(1):32. doi: 10.1186/s13287-019-1137-9.

Abstract

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.

Keywords: Apoptosis; Bcl-2; Ell3; Senescence; Somatic stem cell; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Apoptosis / physiology
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cellular Senescence / physiology
  • Humans
  • MCF-7 Cells
  • Osteocytes / cytology
  • Osteocytes / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transcriptional Activation
  • Transcriptional Elongation Factors / antagonists & inhibitors
  • Transcriptional Elongation Factors / biosynthesis
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • BCL2 protein, human
  • ELL3 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Transcriptional Elongation Factors
  • Tumor Suppressor Protein p53