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Evaluating miR-34c-5p impact in naïve CD4 T cell differentiation using logical modelling
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Resumo(s)
Micro RNAs (miRNAs) are small non-coding single stranded RNAs who act as post-transcriptional
silencers of gene expression through the translational inhibition or degradation of mRNA, being
involved in the regulation of most cellular processes, including haematopoiesis, the differentiation of
multipotential haemotopoietic stem cells into blood cellular components, such as T lymphocyte cells.
CD4+ T helper cells (Th cells), one of two main classes of T lymphocytes, coordinate other immune
system cells, and are further classified in several subtypes, which express different transcription factors
and cytokines and are produced preferentially in different cellular environments.
Logical models (Bornholdt, 2008; Wang et al., 2012) are defined by Logical Regulatory Networks
(LRG), a series of nodes and edges corresponding to the regulatory components of a system (example:
proteins), and the interactions between nodes (example: activations and inhibitions). Nodes are also
associated with discrete variables, which represent their activity level, and logical rules, whose role is
to determine the activity level of a node.
Through the adaptation of a previously published model (Abou-Jaoudé et al., 2015), with new
nodes and interactions, we studied the impact of miR-34c-5p on naïve CD4 T cell differentiation, along
with miR-155-5p (which we use as a control). We found a set of logical rules able to produce all Th cell
subtypes in their preferred environment and analyzed the steady states of the model across thirty-six
different initial conditions, representing different cellular environments.
Thus, we conclude that miR-34c-5p may play an inhibitory role in naïve CD4 T cell differentiation
into Th9 and Th17 cells, a stimulatory role in the formation of Th2, Th22, Tfh and Treg cells, while
playing no role in the formation of Th1 cells. We also found some evidence that miR-34c-5p can inhibit
the effect of miR-155-5p in naïve CD4 T cell differentiation.
Descrição
Tese de mestrado, Bioquímica e Biomedicina, 2025, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
miR-34c-5p miR-155-5p Logical modelling CD4+ T cell differentiation Teses de mestrado - 2025