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Chromatin reader Dido3 regulates the genetic network of B cell differentiation

ABSTRACT: The development of hematopoietic lineages is based on a complex balance of transcription factors whose expression depends on the epigenetic signatures that characterize each differentiation step. The B cell lineage arises from hematopoietic stem cells through the stepwise silencing of stemness genes and balanced expression of mutually regulated transcription factors, as well as DNA rearrangement. Here we report the impact on B cell differentiation of lack of Dido3, a reader of the chromatin status, in the hematopoietic compartment. We found a reduced DNA accessibility in hematopoietic precursors, leading to severe deficiency in the generation of successive B cell differentiation stages. The expression of essential transcription factors and differentiation markers is affected, as is the somatic recombination process.

ORGANISM(S): Mus musculus

PROVIDER: GSE157228 | GEO | 2022/09/29

REPOSITORIES: GEO

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Project description:Collombet2016 - Lymphoid and myeloid cell specification and transdifferentiation This model is described in the article: Logical modeling of lymphoid and myeloid cell specification and transdifferentiation Samuel Collombet, Chris van Oevelen, Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis Thieffry Proceedings of the National Academy of Sciences of the United States of America Abstract: 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. This model is hosted on BioModels Database and identified by: MODEL1610240000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Chromatin reader Dido3 regulates the genetic network of B cell differentiation

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