The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.
EMBO J
; 34(22): 2804-19, 2015 Nov 12.
Article
in En
| MEDLINE
| ID: mdl-26438726
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Astrocytes
/
Inhibitor of Differentiation Proteins
/
Adult Stem Cells
/
Neural Stem Cells
/
Transcription Factor 3
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2015
Document type:
Article
Affiliation country:
Germany