Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells

Stem Cells Dev. 2018 Mar 15;27(6):378-390. doi: 10.1089/scd.2017.0097. Epub 2018 Feb 27.

Abstract

In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (NgbKO-)NSC line. NgbKO-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both enhancing the cell cycle. Based on additional gene ontology enrichment and pathway analyses, we hypothesize that the loss of Ngb affects multiple cellular signaling pathways with the most important being the Akt-Tp53 axis.

Keywords: cell cycle; neural stem cells; neuroglobin; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Down-Regulation / physiology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / metabolism*
  • Neuroglobin / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation / physiology

Substances

  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Nerve Tissue Proteins
  • Neuroglobin
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins c-akt
  • Cdk6 protein, mouse
  • Cyclin-Dependent Kinase 6