Bulletin of the American Physical Society
APS March Meeting 2019
Volume 64, Number 2
Monday–Friday, March 4–8, 2019; Boston, Massachusetts
Session Y51: Physical Mechanisms of Cell Fate Decision Making and Stem Cell Differentiation/ReprogrammingInvited
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Sponsoring Units: DBIO Chair: Wei Wang, Nanjing University Room: BCEC 253A |
Friday, March 8, 2019 11:15AM - 11:51AM |
Y51.00001: Trigger waves in cell signaling Invited Speaker: James Ferrell Untethered cytosolic proteins can move 10 µm or so in a few seconds by simple random walk diffusion. In a typical eukaryotic cell (with a radius of ~10 µm), this is fast enough to allow a cell to respond in a spatially coordinated fashion to many stimuli. Over larger distance scales, regulators are often spread via flow. For example, hormones like insulin and epinephrine make their way around the body via the circulatory system on a time scale of a minute or so, whereas random walk diffusion would take about 500 years. An alternative to flow for long-range biological communication is the trigger wave. Action potentials are trigger waves; so are calcium waves in neurons and fertilized eggs; and so are cAMP waves in aggregating slime molds. |
Friday, March 8, 2019 11:51AM - 12:27PM |
Y51.00002: Stem cell identity and lineage: insights from network theory and dynamical systems Invited Speaker: Philip Greulich What is a (adult) stem cell? This question is still, after decades of debate, not settled yet. In recent years, high-throughput single-cell RNA-sequencing (scRNA-seq) thought to settle this issue by identifying all cell states and differentiation trajectories, yet the thereby discovered high degree of tissue cell heterogeneity even complicated our picture about stem cells and cell lineages. In this talk, I will show how a graph-theoretical view, combined with novel findings from dynamical and stochastic systems, allows to define cell types in a way that greatly simplifies and brings order to the complex web of cell trajectories as yielded by scRNA-seq. It turns out that with this definition many discoveries from stem cell and developmental biology follow "for free", such as an adult stem cell being at the apex of a lineage hierarchy, and the universal features of asymmetric vs. symmetric stem cell divisions that emerge in the form of very few experimentally observed shapes of clone size distributions. Furthermore, we show that in the presence of homeostatic control (crowding feedback), the identity of a stem cell is fully determined by its controlling environment, and theefore cannot be a cell-intrinsic property. |
Friday, March 8, 2019 12:27PM - 1:03PM |
Y51.00003: Waddington landscape and pathways for stem cell differentiation, reprograming and transdifferentiation Invited Speaker: Jin Wang Waddington landscape in biology gives a qualitative picture for understanding differentiation and development. However, the original Waddington landscape picture lacks physical foundations and quantifications. We developed a nonequilibrium landscape and flux theory for quantifying the Waddington landscape for differentiation, reprogramming and transdifferentiation. We found that the landscape for differentiation and development emerges from the underlying gene regulatory interactions with distinct stem cell and differentiated cell state attractors. Furthermore, the pathways for differentiation, reprogramming, and transdifferentiation among the stem cell and differentiation cell state attractors can be quantified. In addition, the kinetic speed of differentiation, reprogramming, and transdifferentiation can be quantified and associated with the landscape topography. We also show that the dynamics of the differentiation, reprogramming, and transdifferentiation processes are determined by both the landscape gradient and the rotational flux. We show that the flux can influence significantly the pathways and the kinetics of these processes. Importantly, flux may also provide a nonequilibrium driving force for the formation of different cell state attractors as the new active matter phases. We apply the landscape and flux theory to several biological differentiation processes including human stem cell development. We also identified the key genes and regulations for the differentiation and reprogramming based on the landscape topography and pathways. The relationship between development and cancer is also explored with the emergence of cancer stem cell state attractor. This study may provide useful clues for the practice of tissue engineering and cancer treatment. |
Friday, March 8, 2019 1:03PM - 1:39PM |
Y51.00004: Setting the epigenetic stage for differentiation: a collective phenomenon Invited Speaker: Steffen Rulands The self-organisation of cells during embryonic development is one of the most intriguing non-equilibrium processes in nature. How do cells coordinate their behaviour in order to build a living organism? Recent technological advances, for example in genomics, for the first time allow us to probe microscopic states of these processes with unprecedented detail. But how can detailed quantitative information on the microscopic scale be translated into a mechanistic understanding of the collective degrees of freedom that determine biological function at the cellular scale? In this talk, I will give the example of epigenetic patterning in early embryonic development to demonstrate how core concepts from non-equilibrium physics can help gain understanding of the collective processes underlying cell fate regulation. |
Friday, March 8, 2019 1:39PM - 2:15PM |
Y51.00005: Intracellular noise level determines ratio control strategy confined by speed-accuracy tradeoff Invited Speaker: Xiaojun Tian Robust and precise ratio control of heterogeneous phenotypes within an isogenic population is essential in the development and differentiation. However, the mechanisms of such ratio control are poorly understood. Here, we employ experimental and mathematical techniques to understand the combined effects of signal induction and gene expression stochasticity on phenotypic multimodality. We identify two strategies to control phenotypic ratios from an initially homogenous population, suitable roughly to high-noise and low-noise intracellular environments, and we show that both can be used to generate precise fractional differentiation. In noisy gene expression contexts, such as those found in bacteria, induction within the circuit’s bistable region is enough to cause noise-induced bimodality within a feasible timeframe. However, in less noisy contexts, such as tightly controlled eukaryotic systems, spontaneous state transitions are rare and hence bimodality needs to be induced with a controlled pulse of induction that falls outside the bistable region. Finally, we show that noise levels, system response time, and ratio tuning accuracy impose tradeoff and limitations on both ratio control strategies, which guides the selection of strategy alternatives. |
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