The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes

Autor: Dietmar Pfeifer, Leandra Plappert, Miriam Hils, Könül Mammadzada, Christian Schachtrup, Kristina Schachtrup, Katharina S. Rauch, Christian Bohrer, Matthias Kirsch, Verónica I. Dumit, Jörn Dengjel, Sebastian Schildge, Lauriane Pous, Sabrina Pfurr
Rok vydání: 2015
Předmět:
Zdroj: The EMBO Journal. 34:2804-2819
ISSN: 1460-2075
0261-4189
DOI: 10.15252/embj.201591118
Popis: 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.
Databáze: OpenAIRE
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