scholarly journals Stem cell competition in the gut: insights from multi-scale computational modelling

2016 ◽  
Vol 13 (121) ◽  
pp. 20160218 ◽  
Author(s):  
Torsten Thalheim ◽  
Peter Buske ◽  
Jens Przybilla ◽  
Karen Rother ◽  
Markus Loeffler ◽  
...  

Three-dimensional (3D) computational tissue models can provide a comprehensive description of tissue dynamics at the molecular, cellular and tissue level. Moreover, they can support the development of hypotheses about cellular interactions and about synergies between major signalling pathways. We exemplify these capabilities by simulation of a 3D single-cell-based model of mouse small intestinal crypts. We analyse the impact of lineage specification, distribution and cellular lifespan on clonal competition and study effects of Notch- and Wnt activation on fixation of mutations within the tissue. Based on these results, we predict that experimentally observed synergistic effects between autonomous Notch- and Wnt signalling in triggering intestinal tumourigenesis originate in the suppression of Wnt-dependent secretory lineage specification by Notch, giving rise to an increased fixation probability of Wnt-activating mutations. Our study demonstrates that 3D computational tissue models can support a mechanistic understanding of long-term tissue dynamics under homeostasis and during transformation.

2020 ◽  
Author(s):  
Rinke J. van Tatenhove-Pel ◽  
Tomaž Rijavec ◽  
Aleš Lapanje ◽  
Iris van Swam ◽  
Emile Zwering ◽  
...  

AbstractMetabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver and competitor cells in different spatial structures. We show that receivers cannot interact with producers ∼15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and created variants of the receiver cells’ import system, to show that within producer-receiver aggregates even low affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces the interaction distance to the low micrometer-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions.


2020 ◽  
Author(s):  
Rinke J. van Tatenhove-Pel ◽  
Tomaž Rijavec ◽  
Aleš Lapanje ◽  
Iris van Swam ◽  
Emile Zwering ◽  
...  

Abstract Metabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional aqueous system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver, and competitor cells in different spatial structures. We show that receivers cannot interact with producers located on average 15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and varied the receiver cells’ product affinity, to show that within producer–receiver aggregates even low-affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces metabolic interaction distances to the low µm-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions.


Author(s):  
J. P. Revel

Movement of individual cells or of cell sheets and complex patterns of folding play a prominent role in the early developmental stages of the embryo. Our understanding of these processes is based on three- dimensional reconstructions laboriously prepared from serial sections, and from autoradiographic and other studies. Many concepts have also evolved from extrapolation of investigations of cell movement carried out in vitro. The scanning electron microscope now allows us to examine some of these events in situ. It is possible to prepare dissections of embryos and even of tissues of adult animals which reveal existing relationships between various structures more readily than used to be possible vithout an SEM.


Author(s):  
Halit Dogan ◽  
Md Mahbub Alam ◽  
Navid Asadizanjani ◽  
Sina Shahbazmohamadi ◽  
Domenic Forte ◽  
...  

Abstract X-ray tomography is a promising technique that can provide micron level, internal structure, and three dimensional (3D) information of an integrated circuit (IC) component without the need for serial sectioning or decapsulation. This is especially useful for counterfeit IC detection as demonstrated by recent work. Although the components remain physically intact during tomography, the effect of radiation on the electrical functionality is not yet fully investigated. In this paper we analyze the impact of X-ray tomography on the reliability of ICs with different fabrication technologies. We perform a 3D imaging using an advanced X-ray machine on Intel flash memories, Macronix flash memories, Xilinx Spartan 3 and Spartan 6 FPGAs. Electrical functionalities are then tested in a systematic procedure after each round of tomography to estimate the impact of X-ray on Flash erase time, read margin, and program operation, and the frequencies of ring oscillators in the FPGAs. A major finding is that erase times for flash memories of older technology are significantly degraded when exposed to tomography, eventually resulting in failure. However, the flash and Xilinx FPGAs of newer technologies seem less sensitive to tomography, as only minor degradations are observed. Further, we did not identify permanent failures for any chips in the time needed to perform tomography for counterfeit detection (approximately 2 hours).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cui Wang ◽  
Ling Cai ◽  
Yaojian Wu ◽  
Yurong Ouyang

AbstractIntegrated renovation projects are important for marine ecological environment protection. Three-dimensional hydrodynamics and water quality models are developed for the Maowei Sea to assess the hydrodynamic environment base on the MIKE3 software with high resolution meshes. The results showed that the flow velocity changed minimally after the project, decreasing by approximately 0.12 m/s in the east of the Maowei Sea area and increasing by approximately 0.01 m/s in the northeast of the Shajing Port. The decrease in tidal prism (~ 2.66 × 106 m3) was attributed to land reclamation, and accounted for just 0.86% of the pre-project level. The water exchange half-life increased by approximately 1 day, implying a slightly reduced water exchange capacity. Siltation occurred mainly in the reclamation and dredging areas, amounting to back-silting of approximately 2 cm/year. Reclamation project is the main factor causing the decrease of tidal volume and weakening the hydrodynamics in Maowei Sea. Adaptive management is necessary for such a comprehensive regulation project. According to the result, we suggest that reclamation works should strictly prohibit and dredging schemes should optimize in the subsequent regulation works.


Minerals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Hamid Ait Said ◽  
Hassan Noukrati ◽  
Hicham Ben Youcef ◽  
Ayoub Bayoussef ◽  
Hassane Oudadesse ◽  
...  

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites were formulated via solid-liquid technic and freeze-drying. The prepared composites had an apatitic nature, which was demonstrated by X-ray diffraction and Infrared spectroscopy analyses. The impact of the solid/liquid (S/L) ratio and the content and the molecular weight of the polymer on the composite mechanical strength was investigated. An increase in the S/L ratio from 0.5 to 1 resulted in an increase in the compressive strength for HA-CSL (CS low molecular weight: CSL) from 0.08 ± 0.02 to 1.95 ± 0.39 MPa and from 0.3 ± 0.06 to 2.40 ± 0.51 MPa for the HA-CSM (CS medium molecular weight: CSM). Moreover, the increase in the amount (1 to 5 wt%) and the molecular weight of the polymer increased the mechanical strength of the composite. The highest compressive strength value (up to 2.40 ± 0.51 MPa) was obtained for HA-CSM (5 wt% of CS) formulated at an S/L of 1. The dissolution tests of the HA-CS composites confirmed their cohesion and mechanical stability in an aqueous solution. Both polymer and apatite are assumed to work together, giving the synergism needed to make effective cylindrical composites, and could serve as a promising candidate for bone repair in the orthopedic field.


2021 ◽  
Vol 22 (2) ◽  
pp. 518
Author(s):  
Adam James Ferrari ◽  
Ronny Drapkin ◽  
Rajan Gogna

Cell competition (CC) is a feature that allows tumor cells to outcompete and eliminate adjacent cells that are deemed less fit. Studies of CC, first described in Drosophila melanogaster, reveal a diversity of underlying mechanisms. In this review, we will discuss three recent studies that expand our understanding of the molecular features governing CC. In particular, we will focus on a molecular fitness fingerprint, oncogenic pathways, and the importance of cell junction stability. A fitness fingerprint, mediated by flower (hFWE) protein isoforms, dictates that cells expressing the flower-win isoforms will outcompete adjacent flower-loss-expressing cells. The impact of the flower protein isoforms is seen in cancer progression and may have diagnostic potential. The yes-associated protein (YAP) and TAZ transcription factors, central mediators of the oncogenic Hippo pathway, elevate peritumoral fitness thereby protecting against tumor progression and provide a suppressive barrier. Similarly, COL17A1 is a key component in hemidesmosome stability, and its expression in epidermal stem cells contributes to fitness competition and aging characteristics. The contributions of these pathways to disease development and progression will help define how CC is hijacked to favor cancer growth. Understanding these features will also help frame the diagnostic and therapeutic possibilities that may place CC in the crosshairs of cancer therapeutics.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Francesco Rizzetto ◽  
Francesca Calderoni ◽  
Cristina De Mattia ◽  
Arianna Defeudis ◽  
Valentina Giannini ◽  
...  

Abstract Background Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs). Methods After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI. Results The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78–0.89) and Hausdorff distance (0.21 mm, 0.14–0.31 mm). Comparing RF values, MRC ranged 0–752% for 2D and 0–1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability. Conclusions A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.


2020 ◽  
Vol 49 (D1) ◽  
pp. D38-D46
Author(s):  
Kyukwang Kim ◽  
Insu Jang ◽  
Mooyoung Kim ◽  
Jinhyuk Choi ◽  
Min-Seo Kim ◽  
...  

Abstract Three-dimensional (3D) genome organization is tightly coupled with gene regulation in various biological processes and diseases. In cancer, various types of large-scale genomic rearrangements can disrupt the 3D genome, leading to oncogenic gene expression. However, unraveling the pathogenicity of the 3D cancer genome remains a challenge since closer examinations have been greatly limited due to the lack of appropriate tools specialized for disorganized higher-order chromatin structure. Here, we updated a 3D-genome Interaction Viewer and database named 3DIV by uniformly processing ∼230 billion raw Hi-C reads to expand our contents to the 3D cancer genome. The updates of 3DIV are listed as follows: (i) the collection of 401 samples including 220 cancer cell line/tumor Hi-C data, 153 normal cell line/tissue Hi-C data, and 28 promoter capture Hi-C data, (ii) the live interactive manipulation of the 3D cancer genome to simulate the impact of structural variations and (iii) the reconstruction of Hi-C contact maps by user-defined chromosome order to investigate the 3D genome of the complex genomic rearrangement. In summary, the updated 3DIV will be the most comprehensive resource to explore the gene regulatory effects of both the normal and cancer 3D genome. ‘3DIV’ is freely available at http://3div.kr.


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