Abstract :
[en] Transcription factor cross-repression is an important concept in cellular differentiation.
A bistable toggle switch constitutes a molecular mechanism that determines cellular
commitment and provides stability to transcriptional programs of binary cell fate choices.
Experiments support that perturbations of these toggle switches can interconvert these
binary cell fate choices, suggesting potential reprogramming strategies. However, more
complex types of cellular transitions could involve perturbations of combinations of
different types of multistable motifs. Here we introduce a method that generalizes the
concept of transcription factor cross-repression to systematically predict sets of genes,
whose perturbations induce cellular transitions between any given pair of cell types.
Furthermore, to our knowledge, this is the first method that systematically makes these
predictions without prior knowledge of potential candidate genes and pathways involved,
providing guidance on systems where little is known. Given the increasing interest of
cellular reprogramming in medicine and basic research, our method represents a useful
computational methodology to assist researchers in the field in designing experimental
strategies.
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