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bioRxiv · 10.1101/2025.03.06.641782

Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks

BV, H.·Billakurthi, H. S.·Adigwe, S.·Hari, K.·Levine, H.·Gedeon, T.·Jolly, M. K.
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Abstract

Stem cell differentiation during development is governed by the dynamics of the underlying gene regulatory networks (GRNs). Mutually inhibiting nodes/collection of nodes encompass the GRNs that govern differentiation to two distinct fates. But the properties of GRNs that can allow differentiation into n-terminal phenotypes are not understood. In this study, we examine toggle-n networks, encompassing mutual inhibitions among multiple transcription factors, to derive generalized conclusions regarding the dynamics underlying differentiation into n-terminal phenotypes. We show that in steady-state distributions of gene expression, multiple cell state-specific transcription factors are co-expressed, indicating an obligatory multi-step process of multi-lineage differentiation. Furthermore, we show that cytokine signaling and specific asymmetry of regulatory links can lead to directed differentiation towards a particular cell state. Our findings provide valuable insights into the mechanistic aspects of directed differentiation of stem cells.

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BV, H., Billakurthi, H. S., Adigwe, S., Hari, K., Levine, H., Gedeon, T., Jolly, M. K.. 2025-03-11. Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks. https://doi.org/10.1101/2025.03.06.641782

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