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

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. ![][1] Our study shows that cortical brain injury causes temporary environmental changes within the subventricular zone (SVZ) stem cell niche, resulting in an altered balance of the transcriptional regulators Id3 and E47 in neural stem/precursor cells (NSPCs), leading to preferential differentiation of NSPCs into astrocytes. The EMBO Journal (2015) 34: 2804–2819 [1]: /embed/graphic-1.gif