Neural stem cells divide during embryogenesis and juvenile life to generate the 
entire complement of neurons and glia in the nervous system of vertebrates and 
invertebrates. Studies of the mechanisms controlling the fine balance between 
neural stem cells and more differentiated progenitors have shown that, in every 
asymmetric cell division, progenitors send a Delta-Notch signal to their sibling 
stem cells. Here, we show that excessive activation of Notch or overexpression 
of its direct targets of the Hes family causes stem-cell hyperplasias in the 
Drosophila larval central nervous system, which can progress to malignant 
tumours after allografting to adult hosts. We combined transcriptomic data from 
these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription 
factor, to identify genes regulated by Hes factors in this process. We show that 
the Notch/Hes axis represses a cohort of transcription factor genes. These are 
excluded from the stem cells and promote early differentiation steps, most 
likely by preventing the reversion of immature progenitors to a stem-cell fate. 
We describe the impact of two of these 'anti-stemness' factors, Zfh1 and Gcm, on 
Notch/Hes-triggered tumorigenesis.