| Autor: |
Bohrer, Christian, Pfurr, Sabrina, Mammadzada, Könül, Schildge, Sebastian, Plappert, Leandra, Hils, Miriam, Pous, Lauriane, Rauch, Katharina S, Dumit, Verónica I, Pfeifer, Dietmar, Dengjel, Jörn, Kirsch, Matthias, Schachtrup, Kristina, Schachtrup, Christian |
| Předmět: |
|
| Zdroj: |
EMBO Journal; 11/12/2015, Vol. 34 Issue 22, p2804-2819, 16p, 6 Graphs |
| Abstrakt: |
Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation. Here, we show that genetic depletion of the transcriptional regulator Id3 decreased the number of astrocytes generated from SVZ-derived adult NSPCs in the cortical lesion area after traumatic brain injury. Cortical brain injury resulted in rapid BMP-2 and Id3 up-regulation in the SVZ stem cell niche. Id3-/- adult NSPCs failed to differentiate into BMP-2-induced astrocytes, while NSPCs deficient for the Id3-controlled transcription factor E47 readily differentiated into astrocytes in the absence of BMP-2. Mechanistically, E47 repressed the expression of several astrocyte-specific genes in adult NSPCs. These results identify Id3 as the BMP-2-induced transcriptional regulator, promoting adult NSPC differentiation into astrocytes upon CNS injury and reveal a molecular link between environmental changes and NSPC differentiation in the CNS after injury. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Plný text