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

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 (Ngb-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (Ngb-)NSC line. Ngb-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.

Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune‐effector functions of interleukin 13‐primed microglia and macrophages in terms of neuroimmune toxicity

“…NSCs were isolated from the embryonic brains of wt C57BL/6 E15 embryos and maintained in neural expansion medium (NEM), as previously described (Luyckx, Van Leuven, et al, 2018; Quarta et al, 2019). In brief, NEM is composed of Neurobasal A medium supplemented with 10 ng/mL epidermal growth factor (EGF; ImmunoTools, Friesoythe, Germany), 10 ng/mL human fibroblast growth factor‐2 (ImmunoTools), 100 U/mL penicillin, 100 mg/mL streptomycin, 0.5 mg/mL Amphotericin B and 1% modified N2 supplement.…”

Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1

“…As an essential effector of canonical Wnt/β-Catenin signaling pathway, Dvl1 is an important regulator in the proliferation and differentiation of neural progenitor cells [ 34 ]. Emerging data suggested that Ngb plays a key role in neurodevelopment and neurogenesis [ 35 ], and a most recent study showed that the loss of Ngb resulted in enhanced cell cycle progression and increased proliferation of neural stem cells [ 36 ]. However, the underlying molecular mechanisms still remain largely unknown.…”

The Yin and Yang of Autosomal Recessive Primary Microcephaly Genes: Insights from Neurogenesis and Carcinogenesis

“…Regulating radial glial cells G1 and S phases [66] DNA damage response, apoptosis (epithelial ovarian cancer) [67] Positively regulates the proliferation of hippocampal progenitors [68] Cell cycle (glioblastoma) [69] Proliferation of neural stem cells [70] Cell cycle, cell proliferation and angiogenesis (hematopoietic malignancies) [71] Cell cycle and apoptosis (T-cell acute lymphoblastic leukemia) [72] MCPH13 (CENPE) N/A Cell G2/M phase and proliferation (lung cancer) [25] MCPH14 (SAS6) N/A Centrosome amplification, mitotic abnormality (CRCs) [73] MCPH15 (MFSD2A) Blood-brain barrier disruption [74] Cell cycle (G1 phase) and matrix attachment (lung cancer) [41] MCPH16 (ANKLE2) Reduced cell proliferation [75] N/A…”