Drawing a Waddington landscape to capture dynamic epigenetics

Nicol-Benoit, Floriane; Goff, Pascale Le; Michel, Denis

doi:10.1111/boc.201300029

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…The intratracheally instilled bone marrow cells did not differentiate into non-hematopoietic cells in the lung. This is consistent with the conventional concept that transdifferentiation is unlikely to occur beyond the germ layer (Nicol-Benoit et al 2013 ; Terada et al 2002 ; Ying et al 2002 ). However, bone marrow cells exhibited similar patterns of surface antigens and similar function of TNF-α production in response to LPS treatment, with residential macrophages, suggesting hematopoietic stem cells progressed to the alveolar macrophage phenotype.…”

Section: Discussionsupporting

confidence: 90%

Alveolar macrophage phenotype expression in airway-instilled bone marrow cells in mice

et al. 2015

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No uniform consensus has been established regarding post-pneumonectomy lung regeneration. This study was undertaken to determine whether airway-instilled lung- or bone marrow-derived cells are able to differentiate and reconstitute as lung component cells in the course of post-pneumonectomy lung growth. Bone marrow cells or lung cells obtained from C57 black (BL)/6-GFP mice were intratracheally instilled into C57BL/6 mice treated with left pneumonectomy and cell differentiation was examined. It is unclear whether intratracheally instilled lung or bone marrow cells differentiate into non-hematopoietic cells after pneumonectomy. However, regardless of whether pneumonectomy is performed, intratracheally instilled bone marrow cells display a surface antigen profile that is similar to alveolar macrophages. Furthermore, these newly differentiated macrophages function similarly to resident macrophages in terms of TNF-α production, suggesting that bone marrow stem cells acquire the same macrophage phenotype. In conclusion, intratracheally instilled bone marrow cells adapt to the surrounding microenvironment, directly differentiating into alveolar macrophages, and remain in the alveolar space for at least 3 months.

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Section: Discussionsupporting

confidence: 90%

Alveolar macrophage phenotype expression in airway-instilled bone marrow cells in mice

et al. 2015

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“…Alternatively, defining an epigenetic landscape or signature has been one approach for defining states (Bonasio et al, 2010; Tronson et al, 2012; Nicol-Benoit et al, 2013). Here, unique epigenetic signatures of histone acetylation, phosphorylation and methylation and DNA methylation during different forms of neuroimmune activation, and that persist after resolution of immune signaling will better define the multiple acute and long-lasting brain states that can be induced by neuroimmune signaling (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Neuroimmune Activation Drives Multiple Brain States

Tchessalova

Posillico

Tronson

2018

Front. Syst. Neurosci.

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Neuroimmune signaling is increasingly identified as a critical component of neuronal processes underlying memory, emotion and cognition. The interactions of microglia and astrocytes with neurons and synapses, and the individual cytokines and immune signaling molecules that mediate these interactions are a current focus of much research. Here, we discuss neuroimmune activation as a mechanism triggering different states that modulate cognitive and affective processes to allow for appropriate behavior during and after illness or injury. We propose that these states lie on a continuum from a naïve homeostatic baseline state in the absence of stimulation, to acute neuroimmune activity and chronic activation. Importantly, consequences of illness or injury including cognitive deficits and mood impairments can persist long after resolution of immune signaling. This suggests that neuroimmune activation also results in an enduring shift in the homeostatic baseline state with long lasting consequences for neural function and behavior. Such different states can be identified in a multidimensional way, using patterns of cytokine and glial activation, behavioral and cognitive changes, and epigenetic signatures. Identifying distinct neuroimmune states and their consequences for neural function will provide a framework for predicting vulnerability to disorders of memory, cognition and emotion both during and long after recovery from illness.

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“…The potential function for this unidimensional landscape can be straightly calculated by integration of the product evolution function (synthesis minus removal) [33,34]. Assuming a time scale separation between the DNA/TF interactions and gene expression dynamics, the rigorous modeling of this minimalist gene circuit, which distinguishes the monomer, dimer and total concentrations of the TF [35], reads…”

Section: Single Gene Circuit: the Self-regulated Gene Encoding A Dimementioning

confidence: 99%

“…To obtain such curves, degradation is generally exponential, with a flux proportional to the product concentration, while synthesis follows a saturable and sigmoidal function of the TFs. This sigmoidicity can be due to a variety of reasons, including TF dimerisation [36,33,35,37], or sequestration by a "poison partner", as in the next example. The resulting landscapes obtained by integration of the evolution function are shown in Fig.5C using the same parameters as above and for various values of b.…”

Section: Single Gene Circuit: the Self-regulated Gene Encoding A Dimementioning

confidence: 99%

The basal level of gene expression associated with chromatin loosening shapes Waddington landscapes and controls cell differentiation

Flouriot

Jehanno

Page

et al. 2019

Preprint

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The baseline level of transcription is variable and seriously complicates the normalization of comparative transcriptomic data, but its biological importance remains unappreciated. We show that this ingredient is in fact crucial for the interpretation of molecular biology results. It is correlated to the degree of chromatin loosening measured by DNA accessibility, and systematically leads to cellular dedifferentiation as assessed by transcriptomic signatures, irrespective of the molecular and cellular tools used. A theoretical analysis of gene circuits formally involved in differentiation, reveals that the epigenetic landscapes of Waddington are restructured by the level of non-specific expression, such that the attractors of progenitor and differentiated cells can be mutually exclusive. Together, these results unveil a generic principle of epigenetic landscape remodeling in which the basal gene expression level, notoriously important in pluripotent cells, allows the maintenance of stemness by generating a specific landscape and in turn, its reduction favors multistability and thereby differentiation. This study highlights how heterochromatin maintenance is essential for preventing pathological cellular reprogramming, age-related diseases and cancer.

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Drawing a Waddington landscape to capture dynamic epigenetics

Cited by 8 publications

References 42 publications

Alveolar macrophage phenotype expression in airway-instilled bone marrow cells in mice

Alveolar macrophage phenotype expression in airway-instilled bone marrow cells in mice

Neuroimmune Activation Drives Multiple Brain States

The basal level of gene expression associated with chromatin loosening shapes Waddington landscapes and controls cell differentiation

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