scholarly journals NF-κB and TNF Affect the Astrocytic Differentiation from Neural Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 840
Author(s):  
Cindy Birck ◽  
Aurélien Ginolhac ◽  
Maria Angeliki S. Pavlou ◽  
Alessandro Michelucci ◽  
Paul Heuschling ◽  
...  

The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells (NPCs). Here, we provide evidence  that the NF-κB pathway plays also a fundamental role during the differentiation of NPCs into astrocytes. First, we show that the NF-κB pathway is essential to initiate astrocytic differentiation as its early inhibition induces NPC apoptosis and impedes their differentiation. Second, we demonstrate that persistent NF-κB activation affects NPC-derived astrocyte differentiation. Tumor necrosis factor (TNF)-treated NPCs show NF-κB activation, maintain their multipotential and proliferation properties, display persistent expression of immature markers and inhibit astrocyte markers. Third, we analyze the effect of  NF-κB activation on the main known astrocytic differentiation pathways, such as NOTCH and JAK-STAT. Our findings suggest that the NF-κB pathway plays a dual fundamental role during NPC differentiation into astrocytes: it promotes astrocyte specification, but its persistent activation impedes their differentiation.

2015 ◽  
Vol 117 (1) ◽  
pp. 180-196 ◽  
Author(s):  
Ekaterina S. Zubkova ◽  
Irina B. Beloglazova ◽  
Pavel I. Makarevich ◽  
Maria A. Boldyreva ◽  
Olga Yu. Sukhareva ◽  
...  

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2806-2812 ◽  
Author(s):  
Steven F. A. Weekx ◽  
Hans W. Snoeck ◽  
Fritz Offner ◽  
Magda De Smedt ◽  
Dirk R. Van Bockstaele ◽  
...  

To investigate the T-lymphopoietic capacity of human adult bone marrow (ABM) hematopoietic progenitor cells, CD34+Lin−, CD34+CD38+, and CD34++CD38− cells were cultured in a severe combined immunodeficient (SCID) mouse fetal thymic organ culture (FTOC). Direct seeding of these progenitors resulted in a moderate to severe cell loss, particularly for the CD34++CD38− cell fraction, and T cells could only be generated from the CD34+Lin− fraction. Preincubation for 36 hours with interleukin-3 (IL-3) and stem cell factor (SCF) led to an improved cell survival and proliferation, although T-cell development was seen only in the CD34+Lin− fraction. Addition of tumor necrosis factor (TNF)- to IL-3 + SCF-supplemented preincubation medium resulted in optimal cell survival, cell proliferation. and T-cell generation of all 3 cell fractions. The TNF- effect resulted in an up-regulation of CD127 (ie, the IL-7 receptor -chain) in a small subset of the CD34+ cells. No evidence could be generated to support the possibility that TNF- inhibits a cell population that suppresses T-cell differentiation. A quantitatively different T-cell generation potency was still seen between the 3 subpopulations: CD34+Lin− (100% success rate) > CD34+CD38+ (66%) > CD34++CD38− (25%). These data contrast with our previous findings using fetal liver and cord blood progenitors, which readily differentiate into T-lymphocytes in FTOC, even without prestimulation with cytokines. Our results demonstrate that adult CD34++CD38− cells, known to contain hematopoietic stem cells, can differentiate into T-lymphocytes and that a significant difference exists in T-lymphopoietic activity of stem cells derived from ontogenetically different sources.


2007 ◽  
Vol 8 (S1) ◽  
Author(s):  
Darius Widera ◽  
Ilja Mikenberg ◽  
Margitta Elvers ◽  
Christian Kaltschmidt ◽  
Barbara Kaltschmidt

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