In addition, when these transcription factors lose their function,
terminal differentiation into the vascular endothelium (completion of differentiation) is completely suppressed, and genes that are key to differentiation into vascular endothelial cells as well as transcription factors that maintain the undifferentiated state are adversely induced.
During embryonic development, neurogenesis proceeds maintaining a fine balance between mechanisms that support self renewal of undifferentiated radial progenitors and others that instruct precursors to commit to specific fates and
achieve terminal differentiation.
A. Cartoon of each
cell terminal differentiation mechanism (Ruler in gray, Timer in pink, and Sizer in red) and (right) juxtaposed (red lines) confocal images of an 8 ‐ day ‐ old WT seedling with the zones being indicated.
E1A is the sole oncogene capable of overcoming the stringent proliferative block connected
with terminal differentiation, likely due to E1A - induced mimicry of important proliferation and dedifferentiation pathways, which are prime candidates for cancer pathways (24).
The scientists conclude that the study reveals an essential function for CTCF in the orchestration of transcriptional changes during
the terminal differentiation of B lymphocytes and advances understanding of the mechanisms that regulate the immune response.
Pioneering work by Barrandon and Green more than 20 years ago (2) showed that when primary human keratinocytes were put in culture, their abilities to establish a clone were related to the heterogeneity in cell size — only cells ≤ 11 μm in diameter could form a clone whereas cells ≥ 12 μm were irreversibly committed to
terminal differentiation.
We further demonstrate that one mechanism by which the reversibility of quiescence is insured is the suppression of
terminal differentiation.
For this project, we will use this property against the tumor by modulating factors that support the self - renewal of the stem cell compartment and by inducing
their terminal differentiation along alternate pathways that have reduced malignant potential.