Biology

Dr. Neha Tiwari
Johannes Gutenberg University Mainz

It is increasingly clear that a coordinated crosstalk between transcription factors and epigenetic mechanisms plays a key role in cell-fate decisions during development and is a target of misregulation in many diseases such as cancer. Despite advances, these aspects of the gene regulatory mechanisms that steer neural stem cells towards astrocytes during brain development are largely unknown. Here we set out to comprehensively identify transcription factors that drive the developmental trajectory of astrogliogenesis from mouse embryonic stem cells. To attain this we performed a genomewide analysis of gene expression and epigenetic signature hallmarks of primed and active enhancers through the distinct stages of astrogliogenesis. We revealed distal regulatory elements that become activated in a stage-specific manner which confer the transcriptional program underlying generation and maturation of astrocytes. By searching for lineage-specific transcription factors functioning at these elements, we identified transcription factors that drive differentiation of neural precursor cells to astrocytes and their maturation. These transcription factors are crucial for switching the chromatin state of these elements from primed to active, thereby driving the gene expression program underlying astrocyte differentiation and maturation. Furthermore, identification of these transcription factors paves a way to cure astrocyte related neurological diseases where astrocytes get dysfunction during development.