A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells

Ruiz-Perera LM, Greiner J, Kaltschmidt C, Kaltschmidt B (2020)
Cells 9(4): 1037.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
The molecular mechanisms underlying fate decisions of human neural stem cells (hNSCs) between neurogenesis and gliogenesis are critical during neuronal development and neurodegenerative diseases. Despite its crucial role in the murine nervous system, the potential role of the transcription factor NF-κB in the neuronal development of hNSCs is poorly understood. Here, we analyzed NF-κB subunit distribution during glutamatergic differentiation of hNSCs originating from neural crest-derived stem cells. We observed several peaks of specific NF-κB subunits. The most prominent nuclear peak was shown by c-REL subunit during a period of 2–5 days after differentiation onset. Furthermore, c-REL inhibition with pentoxifylline (PTXF) resulted in a complete shift towards oligodendroglial fate, as demonstrated by the presence of OLIG2+/O4+-oligodendrocytes, which showed PDGFRα, NG2 and MBP at the transcript level. In addition c-REL impairment further produced a significant decrease in neuronal survival. Transplantation of PTXF-treated predifferentiated hNSCs into an ex vivo oxidative-stress-mediated demyelination model of mouse organotypic cerebellar slices further led to integration in the white matter and differentiation into MBP+ oligodendrocytes, validating their functionality and therapeutic potential. In summary, we present a human cellular model of neuronal differentiation exhibiting a novel essential function of NF-κB-c-REL in fate choice between neurogenesis and oligodendrogenesis which will potentially be relevant for multiple sclerosis and schizophrenia. View Full-Text
Stichworte
NF-κB-c-REL; oligodendroglial fate shift; pentoxifylline; MBP; survival
Erscheinungsjahr
2020
Zeitschriftentitel
Cells
Band
9
Ausgabe
4
Art.-Nr.
1037
eISSN
2073-4409
Page URI
https://pub.uni-bielefeld.de/record/2942915

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Ruiz-Perera LM, Greiner J, Kaltschmidt C, Kaltschmidt B. A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells. 2020;9(4): 1037.
Ruiz-Perera, L. M., Greiner, J., Kaltschmidt, C., & Kaltschmidt, B. (2020). A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells, 9(4), 1037. doi:10.3390/cells9041037
Ruiz-Perera, L. M., Greiner, J., Kaltschmidt, C., and Kaltschmidt, B. (2020). A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells 9:1037.
Ruiz-Perera, L.M., et al., 2020. A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells, 9(4): 1037.
L.M. Ruiz-Perera, et al., “A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells”, Cells, vol. 9, 2020, : 1037.
Ruiz-Perera, L.M., Greiner, J., Kaltschmidt, C., Kaltschmidt, B.: A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells. 9, : 1037 (2020).
Ruiz-Perera, Lucia Mercedes, Greiner, Johannes, Kaltschmidt, Christian, and Kaltschmidt, Barbara. “A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells”. Cells 9.4 (2020): 1037.
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2020-04-27T07:30:02Z
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