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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

Logical modeling of lymphoid and myeloid cell specification and transdifferentiation

Résumé

Blood cells are derived from a common set of hematopoietic stem cells, which differentiate into more specific progenitors of the myeloid and lymphoid lineages, ultimately leading to differentiated cells. This developmental process is controlled by a complex regulatory network involving cytokines and their receptors, transcription factors, and chromatin remodelers. Using public data and data from our own molecular genetic experiments (quantitative PCR, Western blot, EMSA) or genome-wide assays (RNA-sequencing, ChIP-sequencing), we have assembled a comprehensive regulatory network encompassing the main transcription factors and signaling components involved in myeloid and lymphoid development. Focusing on B-cell and macrophage development, we defined a qualitative dynamical model recapitulating cytokine-induced differentiation of common progenitors, the effect of various reported gene knockdowns, and the reprogramming of pre-B cells into macrophages induced by the ectopic expression of specific transcription factors. The resulting network model can be used as a template for the integration of new hematopoietic differentiation and transdifferentiation data to foster our understanding of lymphoid/myeloid cell-fate decisions.

Dates et versions

hal-03352074 , version 1 (23-09-2021)

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Citer

Samuel Collombet, Chris van Oevelen, Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di Stefano, et al.. Logical modeling of lymphoid and myeloid cell specification and transdifferentiation. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (23), pp.5792-5799. ⟨10.1073/pnas.1610622114⟩. ⟨hal-03352074⟩

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