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Wendy L. Havran, PhD: 1955–2020
Article

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

1
Molecular Neurobiology, University of Bielefeld, 33615 Bielefeld, Germany
2
Department of Cell Biology, University of Bielefeld, 33615 Bielefeld, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 1037; https://doi.org/10.3390/cells9041037
Received: 16 March 2020 / Revised: 18 April 2020 / Accepted: 20 April 2020 / Published: 22 April 2020
(This article belongs to the Special Issue Neural Stem Cell Systems to Study Brain Development and Diseases)
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
Keywords: NF-κB-c-REL; oligodendroglial fate shift; pentoxifylline; MBP; survival NF-κB-c-REL; oligodendroglial fate shift; pentoxifylline; MBP; survival
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MDPI and ACS Style

Ruiz-Perera, L.M.; Greiner, J.F.W.; Kaltschmidt, C.; Kaltschmidt, B. A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells. Cells 2020, 9, 1037. https://doi.org/10.3390/cells9041037

AMA Style

Ruiz-Perera LM, Greiner JFW, 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. https://doi.org/10.3390/cells9041037

Chicago/Turabian Style

Ruiz-Perera, Lucia M., Johannes F.W. Greiner, Christian Kaltschmidt, and Barbara Kaltschmidt. 2020. "A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells" Cells 9, no. 4: 1037. https://doi.org/10.3390/cells9041037

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