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  1. Book ; Online: Field theory of enzyme-substrate systems with restricted long-range interactions

    Olmeda, Fabrizio / Rulands, Steffen

    2024  

    Abstract: Enzyme-substrate kinetics form the basis of many biomolecular processes. The interplay between substrate binding and substrate geometry can give rise to long-range interactions between enzyme binding events. Here, we study a general model of enzyme- ... ...

    Abstract Enzyme-substrate kinetics form the basis of many biomolecular processes. The interplay between substrate binding and substrate geometry can give rise to long-range interactions between enzyme binding events. Here, we study a general model of enzyme-substrate kinetics with restricted long-range interactions described by an exponent $-\lambda$. We employ a coherent-state path integral and renormalization group approach to calculate the first moment and two-point correlation function of the enzyme-binding profile. We show that starting from an empty substrate the average occupancy follows a power law with an exponent $1/(1-\lambda)$ over time. The correlation function decays algebraically with two distinct spatial regimes characterized by exponents $-\lambda$ on short distances and $-(2/3)(2-\lambda)$ on long distances. The crossover between both regimes scales inversely with the average substrate occupancy. Our work allows to associate experimental measurements of bound enzyme locations with their binding kinetics and the spatial confirmation of the substrate.
    Keywords Physics - Biological Physics ; Condensed Matter - Statistical Mechanics
    Subject code 612
    Publishing date 2024-01-18
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Book ; Online: Clonal dynamics of surface-driven growing tissues

    Mukhamadiarov, Ruslan / Ciarchi, Matteo / Olmeda, Fabrizio / Rulands, Steffen

    2023  

    Abstract: The self-organization of cells into complex tissues relies on a tight coordination of cell behavior. Identifying the cellular processes driving tissue growth is key for understanding the emergence of tissue forms and for devising targeted therapies for ... ...

    Abstract The self-organization of cells into complex tissues relies on a tight coordination of cell behavior. Identifying the cellular processes driving tissue growth is key for understanding the emergence of tissue forms and for devising targeted therapies for aberrant growth, such as in cancer. Inferring the mode of tissue growth, whether it is driven by cells on the surface or cells in the bulk, is possible in cell culture experiments, but difficult in most tissues in living organisms (in vivo). Genetic tracing experiments, where a subset of cells is labelled with inheritable markers have become important experimental tools to study cell fate in vivo. Here, we show that the mode of tissue growth is reflected in the size distribution of the progeny of marked cells. To this end, we derive the clone-size distributions using analytical calculations and an agent-based stochastic sampling technique in the limit of negligible cell migration and cell death. We show that for surface-driven growth the clone-size distribution takes a characteristic power-law form with an exponent determined by fluctuations of the tissue surface. Our results allow for the inference of the mode of tissue growth from genetic tracing experiments.
    Keywords Quantitative Biology - Quantitative Methods ; Physics - Biological Physics ; Quantitative Biology - Cell Behavior ; Quantitative Biology - Tissues and Organs
    Subject code 612
    Publishing date 2023-12-04
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Compartmentalization and synergy of osteoblasts drive bone formation in the regenerating fin.

    Cudak, Nicole / López-Delgado, Alejandra Cristina / Rost, Fabian / Kurth, Thomas / Lesche, Mathias / Reinhardt, Susanne / Dahl, Andreas / Rulands, Steffen / Knopf, Franziska

    iScience

    2024  Volume 27, Issue 2, Page(s) 108841

    Abstract: Zebrafish regenerate their fins which involves a component of cell plasticity. It is currently unclear how regenerate cells divide labor to allow for appropriate growth and patterning. Here, we studied lineage relationships of fluorescence-activated cell ...

    Abstract Zebrafish regenerate their fins which involves a component of cell plasticity. It is currently unclear how regenerate cells divide labor to allow for appropriate growth and patterning. Here, we studied lineage relationships of fluorescence-activated cell sorting-enriched epidermal, bone-forming (osteoblast), and (non-osteoblast) blastemal fin regenerate cells by single-cell RNA sequencing, lineage tracing, targeted osteoblast ablation, and electron microscopy. Most osteoblasts in the outgrowing regenerate derive from
    Language English
    Publishing date 2024-01-08
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.108841
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Active turnover of DNA methylation during cell fate decisions.

    Parry, Aled / Rulands, Steffen / Reik, Wolf

    Nature reviews. Genetics

    2020  Volume 22, Issue 1, Page(s) 59–66

    Abstract: DNA methylation is a key layer of epigenetic regulation. The deposition of methylation marks relies on the catalytic activity of DNA methyltransferases (DNMTs), and their active removal relies on the activity of ten-eleven translocation (TET) enzymes. ... ...

    Abstract DNA methylation is a key layer of epigenetic regulation. The deposition of methylation marks relies on the catalytic activity of DNA methyltransferases (DNMTs), and their active removal relies on the activity of ten-eleven translocation (TET) enzymes. Paradoxically, in important biological contexts these antagonistic factors are co-expressed and target overlapping genomic regions. The ensuing cyclic biochemistry of cytosine modifications gives rise to a continuous, out-of-thermal equilibrium transition through different methylation states. But what is the purpose of this intriguing turnover of DNA methylation? Recent evidence demonstrates that methylation turnover is enriched at gene distal regulatory elements, including enhancers, and can give rise to large-scale oscillatory dynamics. We discuss this phenomenon and propose that DNA methylation turnover might facilitate key lineage decisions.
    MeSH term(s) Cell Lineage ; Cytosine/metabolism ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Humans ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism
    Chemical Substances DNA-Binding Proteins ; Proto-Oncogene Proteins ; Cytosine (8J337D1HZY) ; Mixed Function Oxygenases (EC 1.-) ; TET1 protein, human (EC 1.-) ; TET2 protein, human (EC 1.13.11.-) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37)
    Language English
    Publishing date 2020-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2035157-4
    ISSN 1471-0064 ; 1471-0056
    ISSN (online) 1471-0064
    ISSN 1471-0056
    DOI 10.1038/s41576-020-00287-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy.

    van der Weijden, Vera A / Stötzel, Maximilian / Iyer, Dhanur P / Fauler, Beatrix / Gralinska, Elzbieta / Shahraz, Mohammed / Meierhofer, David / Vingron, Martin / Rulands, Steffen / Alexandrov, Theodore / Mielke, Thorsten / Bulut-Karslioglu, Aydan

    Nature cell biology

    2024  Volume 26, Issue 2, Page(s) 181–193

    Abstract: Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is ...

    Abstract Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is not known. Here we show that mouse embryos in diapause are sustained by using lipids as primary energy source. In vitro, supplementation of embryos with the metabolite L-carnitine balances lipid consumption, puts the embryos in deeper dormancy and boosts embryo longevity. We identify FOXO1 as an essential regulator of the energy balance in dormant embryos and propose, through meta-analyses of dormant cell signatures, that it may be a common regulator of dormancy across adult tissues. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues.
    MeSH term(s) Animals ; Mice ; Embryo, Mammalian ; Embryonic Development/physiology ; Energy Metabolism ; Lipid Metabolism ; Mammals
    Chemical Substances Foxo1 protein, mouse
    Language English
    Publishing date 2024-01-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/s41556-023-01325-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online ; Thesis: Heterogeneity and spatial correlations in stochastic many-particle systems

    Rulands, Steffen

    from embryogenesis to evolution

    2013  

    Author's details Steffen Rulands
    Language English
    Size Online-Ressource, Ill., graph. Darst.
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Kumulative , Diss.--München, 2013
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  7. Book ; Online ; Thesis: Heterogeneity and spatial correlations in stochastic many-particle systems

    Rulands, Steffen

    from embryogenesis to evolution

    2013  

    Author's details Steffen Rulands
    Language English
    Size Online-Ressource, Ill., graph. Darst.
    Document type Book ; Online ; Thesis
    Thesis / German Habilitation thesis Univ., Kumulative , Diss.--München, 2013
    Database Former special subject collection: coastal and deep sea fishing

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  8. Article ; Online: Tracing cellular dynamics in tissue development, maintenance and disease.

    Rulands, Steffen / Simons, Benjamin D

    Current opinion in cell biology

    2016  Volume 43, Page(s) 38–45

    Abstract: The coordination of cell proliferation and differentiation is central to the development and maintenance of tissues, while its dysregulation underlies the transition to diseased states. By combining lineage tracing with transcriptional profiling and ... ...

    Abstract The coordination of cell proliferation and differentiation is central to the development and maintenance of tissues, while its dysregulation underlies the transition to diseased states. By combining lineage tracing with transcriptional profiling and marker-based assays, statistical methods are delivering insights into the dynamics of stem cells and their developmental precursors. These studies have provided evidence for molecular heterogeneity and fate priming, and have revealed a role for stochasticity in stem cell fate, refocusing the search for regulatory mechanisms. At the same time, they present a quantitative platform to study the initiation and progression of disease. Here, we review how quantitative lineage tracing strategies are shaping our understanding of the cellular mechanisms of tissue development, maintenance and disease.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Cell Lineage ; Cells/pathology ; Disease ; Humans ; Organogenesis ; Stem Cells/cytology
    Language English
    Publishing date 2016-07-27
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2016.07.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Deterministic fate assignment of Müller glia cells in the zebrafish retina suggests a clonal backbone during development.

    Rulands, Steffen / Iglesias-Gonzalez, Ana Belen / Boije, Henrik

    The European journal of neuroscience

    2018  Volume 48, Issue 12, Page(s) 3597–3605

    Abstract: The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate ... ...

    Abstract The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post-fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis.
    MeSH term(s) Animals ; Animals, Genetically Modified/genetics ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; Ependymoglial Cells/metabolism ; Neurogenesis/physiology ; Neuroglia/metabolism ; Neurons/metabolism ; Retina/metabolism ; Stem Cells/metabolism ; Zebrafish/metabolism ; Zebrafish Proteins/metabolism
    Chemical Substances Zebrafish Proteins
    Language English
    Publishing date 2018-11-08
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.14257
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Self-organization of plasticity and specialization in a primitively social insect.

    Patalano, Solenn / Alsina, Adolfo / Gregorio-Rodríguez, Carlos / Bachman, Martin / Dreier, Stephanie / Hernando-Herraez, Irene / Nana, Paulin / Balasubramanian, Shankar / Sumner, Seirian / Reik, Wolf / Rulands, Steffen

    Cell systems

    2022  Volume 13, Issue 9, Page(s) 768–779.e4

    Abstract: Biological systems have the capacity to not only build and robustly maintain complex structures but also to rapidly break up and rebuild such structures. Here, using primitive societies of Polistes wasps, we show that both robust specialization and rapid ...

    Abstract Biological systems have the capacity to not only build and robustly maintain complex structures but also to rapidly break up and rebuild such structures. Here, using primitive societies of Polistes wasps, we show that both robust specialization and rapid plasticity are emergent properties of multi-scale dynamics. We combine theory with experiments that, after perturbing the social structure by removing the queen, correlate time-resolved multi-omics with video recordings. We show that the queen-worker dimorphism relies on the balance between the development of a molecular queen phenotype in all insects and colony-scale inhibition of this phenotype via asymmetric interactions. This allows Polistes to be stable against intrinsic perturbations of molecular states while reacting plastically to extrinsic cues affecting the whole society. Long-term stability of the social structure is reinforced by dynamic DNA methylation. Our study provides a general principle of how both specialization and plasticity can be achieved in biological systems. A record of this paper's transparent peer review process is included in the supplemental information.
    MeSH term(s) Animals ; DNA Methylation ; Phenotype ; Wasps/genetics
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2022.08.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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