The epigenetic landscape in the course of time: Conrad Hal Waddington’s methodological impact on the life sciences

Baedke, Jan

doi:10.1016/j.shpsc.2013.06.001

Cited by 129 publications

(38 citation statements)

References 87 publications

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“…In the early 1940s, Conrad Hal Waddington used the term epigenetic, epi (above) and genetics (genetic), for the first time. 1 An epigenetic modification is defined as any potentially stable and, ideally, heritable change in gene expression or cellular phenotype that occurs without changes in Watson-Crick base-pairing of DNA. 2 The most described epigenetic regulations included chromatin compaction, DNA methylation, histone acetylation/deacetylation, and the noncoding sequences of RNA.…”

Section: Epigeneticsmentioning

confidence: 99%

Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

et al. 2015

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ABSTRACT:Epigenetic modifications have emerged as a new, important contributor to gene expression regulation in both normal and pathophysiological conditions. Epigenetics have been studied in many diseases and conditions such as acute kidney injury (AKI), a syndrome with a high prevalence that carries a poor prognosis with increased morbidity and mortality. In addition, it has recently been shown that AKI increases the risk for the development of chronic kidney disease (CKD). The specific molecular mechanisms by which AKI increases the risk of CKD and end stage renal disease (ESRD) remain unknown, although there is new evidence supporting a role of epigenetic changes. The most studied epigenetic regulations in AKI are chromatin compaction, DNA methylation, and histone acetylation/deacetylation. These modifications predominantly increase the production of proinflammatory and profibrotic cytokines such as: monocyte chemoattractant protein-1 (MCP-1), complement protein 3 (C3), transforming growth factor β (TGF-β) that have been shown for perpetuating inflammation, promoting epithelial-to-mesenchymal transition (EMT) and ultimately causing renal fibrosis. A review of epigenetic mechanisms, the pathophysiology of AKI and recent studies that implicate epigenetic modifications in AKI and in the transition to CKD are discussed below.

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Section: Epigeneticsmentioning

confidence: 99%

Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

et al. 2015

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“…Landscapes of behavioral attractors can be used to represent these macroscopic dynamics (Figure 5). For instance, the epigenetic landscape initially introduced by Waddington (1942, 1957) has been subsequently popularized in development literature by Muchisky et al (1996), and is now used in numerous domains (e.g., Aimetti, 2009; see Baedke (2013), for overview and discussion).…”

Section: A Coordination Dynamics Perspective On Neuro-behavioral Agingmentioning

confidence: 99%

Aging induced loss of complexity and dedifferentiation: consequences for coordination dynamics within and between brain, muscular and behavioral levels

Sleimen-Malkoun

Temprado

Hong

2014

Front. Aging Neurosci.

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Growing evidence demonstrates that aging not only leads to structural and functional alterations of individual components of the neuro-musculo-skeletal system (NMSS) but also results in a systemic re-organization of interactions within and between the different levels and functional domains. Understanding the principles that drive the dynamics of these re-organizations is an important challenge for aging research. The present Hypothesis and Theory paper is a contribution in this direction. We propose that age-related declines in brain and behavior that have been characterized in the literature as dedifferentiation and the loss of complexity (LOC) are: (i) synonymous; and (ii) integrated. We argue that a causal link between the aforementioned phenomena exists, evident in the dynamic changes occurring in the aging NMSS. Through models and methods provided by a dynamical systems approach to coordination processes in complex living systems, we: (i) formalize operational hypotheses about the general principles of changes in cross-level and cross-domain interactions during aging; and (ii) develop a theory of the aging NMSS based on the combination of the frameworks of coordination dynamics (CD), dedifferentiation, and LOC. Finally, we provide operational predictions in the study of aging at neural, muscular, and behavioral levels, which lead to testable hypotheses and an experimental agenda to explore the link between CD, LOC and dedifferentiation within and between these different levels.

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“…Waddington advanced the “epigenetic landscape” during the 40s to visualize the various developmental pathways a cell might take toward differentiation (192). Similarly, the immunological landscape could offer a vivid representation of how fluctuating environmental force during lifetime may alter the evolutionarily fixed genetic response to an immune stimulus (193) (Figure 1). Furthermore, both the epigenetic and immunological landscape stress the dynamic view of ontogenetic (biographical) selective pressure represented by multidimensional aspects of time, space, and context (valleys, bifurcations, attractors).…”

Section: Conclusion and Perspective: Toward A New Conceptualization Omentioning

confidence: 99%

Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

et al. 2014

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The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of “liquid self,” which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body’s ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call “immunological biography.” Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between “self” and “non-self” states in a dynamical, “liquid” fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host.

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The epigenetic landscape in the course of time: Conrad Hal Waddington’s methodological impact on the life sciences

Cited by 129 publications

References 87 publications

Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

Aging induced loss of complexity and dedifferentiation: consequences for coordination dynamics within and between brain, muscular and behavioral levels

Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

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