Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid- or gel-like behavior of chromatin

Chromosome organization and dynamics are involved in regulating many fundamental processes such as gene transcription and DNA repair. Experiments unveiled that chromatin motion is highly heterogeneous inside cell nuclei, ranging from a liquid-like, mobile state to a gel-like, rigid regime. Using polymer modeling, we investigate how these different physical states and dynamical heterogeneities may emerge from the same structural mechanisms. We found that the formation of topologically associating domains (TADs) is a key driver of chromatin motion heterogeneity. In particular, we showed that the local degree of compaction of the TAD regulates the transition from a weakly compact, fluid state of chromatin to a more compact, gel state exhibiting anomalous diffusion and coherent motion. Our work provides a comprehensive study of chromosome dynamics and a unified view of chromatin motion enabling interpretation of the wide variety of dynamical behaviors observed experimentally across different biological conditions, suggesting that the “liquid” or “solid” state of chromatin are in fact two sides of the same coin.

Download Full-text

ЛАНДШАФТНАЯ ОРГАНИЗАЦИЯ БЕРЕГОВОЙ ГЕОСТРУКТУРЫ ОСТРОВА ШКОТА (ЗАЛИВ ПЕТРА ВЕЛИКОГО)

10.33833/tig.2019.65.23.006 ◽

2019 ◽

Author(s):

K.S. Ganzei ◽

V.V. Zharikov ◽

N.F. Pshenichnikova ◽

A.M. Lebedev ◽

A.G. Kiselyova ◽

...

Keyword(s):

Spatial Organization ◽

Peter The Great Bay ◽

Spatial Arrangement ◽

Water Area ◽

Marine Spatial Planning ◽

Landscape Approach ◽

Important Condition ◽

Statistical Comparison ◽

Peter The Great ◽

Comprehensive Study

Важнейшим условием достижения устойчивого развития прибрежноморского природопользования в заливе Петра Великого системы является морское пространственное планирование. Основой для этого является информация о природных комплексах территории и акватории, полученная на основе ландшафтного подхода. Ключевым районом для изучения пространственной организации ландшафтов прибрежных геоструктур стала территория острова Шкота и его подводных склонов. Для наземных ландшафтов было описано 49 наблюдательных пунктов, 4 профиля были заложены для подводных ландшафтов описано 64 наблюдательных пункта, проложено 18 профилей. Выделено 22 вида ландшафтов, из них 16 наземных, 6 подводных. Берега острова сформированы преобладанием абразивноденудационного и абразивного типов. В результате всестороннего изучения показаны особенности пространственной организации воздушных и водных природных комплексов. Особенностью исследуемой территории является экспозиция дифференциации ландшафтов между юговосточной и северозападной частями острова, обусловленная муссонной природой климата. Результаты полевых и картографических работ послужили основой для выбора зон интенсивного, умеренного и ослабленного взаимодействия наземных и подводных ландшафтов. Пространственное расположение зон взаимодействия четко иллюстрируется значительными различиями экспозиции. Результаты статистического сравнения ландшафтов суши и мелководья, окружающего остров, на основе картометрических характеристик указывают на неоднородность геоструктуры острова, обусловленную, прежде всего, сочетанием ландшафтообразующих факторов. The most important condition for achieving sustainable development of coastalmarine environmental management in Peter the Great Bay is marine spatial planning. The basis for this is information about the natural complexes of the territory and water area, obtained based on the landscape approach. The main area for studying the spatial organization of landscapes of coastal geostructures was the territory of the island of Shkota and its underwater slopes. For terrestrial landscapes, 49 observation points were described, 4 profiles were laid 64 observation points were described for underwater landscapes, 18 profiles were laid. 22 species of landscapes have been identified, of which 16 are terrestrial, 6 are underwater. The shores of the island are formed by the predominance of abrasivedenudation and abrasive types. Because of a comprehensive study, features of the spatial organization of air and aquatic natural complexes are shown. A special feature of the study area is the exposure of the differentiation of landscapes between the southeastern and northwestern parts of the island, due to the monsoon nature of the climate. The results of field and cartographic works served as the basis for selecting areas of intense, moderate and weakened interaction of land and underwater landscapes. The spatial arrangement of the interaction zones is clearly illustrated by significant differences in exposure. The results of a statistical comparison of the land and shallow water landscapes surrounding the island, based on the cartometric characteristics, indicate the heterogeneity of the islands geostructure, primarily due to the combination of landscapeforming factors.

Download Full-text

Basement membrane and interstitial matrix components form separate matrices in heterokaryons of PYS-2 cells and fibroblasts

Journal of Cell Science ◽

10.1242/jcs.104.1.59 ◽

1993 ◽

Vol 104 (1) ◽

pp. 59-68

Author(s):

P. Laurila ◽

I. Leivo

Keyword(s):

Basement Membrane ◽

Matrix Protein ◽

Spatial Organization ◽

Gene Dosage ◽

Parental Cell ◽

Cell Nuclei ◽

Fibronectin Matrix ◽

Basement Membrane Protein ◽

The Matrix

In order to gain further understanding of the spatial organization of interstitial and basement membrane matrices, we studied the expression of the interstitial matrix protein, fibronectin, and the basement membrane protein, laminin, in heterokaryons formed by the fusion of normal fibroblasts and teratocarcinoma-derived epithelial PYS-2 cells. These heterokaryons showed various distributions of the matrix proteins depending on the proportions of the different parental cell nuclei within the cytoplasm of the cell. Heterokaryons containing equal numbers of fibroblast and PYS-2 cell nuclei showed an abundant laminin matrix subcellularly and only minor amounts of fibronectin matrix at the periphery of the cells. Similar results were obtained in heterokaryons containing an excess of epithelial cell nuclei. In heterokaryons containing an excess of fibroblast nuclei, on the other hand, laminin matrix was reduced and a fibrillar fibronectin matrix was seen also on top of the cell body. The results suggest a gene dosage-type of effect on the expression of these proteins. Furthermore, extracellular laminin and fibronectin matrices did not codistribute around the heterokaryons but the two proteins were assembled into separate structures. The lack of codistribution of fibronectin and laminin matrices in heterokaryons suggests that the molecular interactions, which determine the assembly of basement membrane and interstitial matrices in these cells are highly type-specific. Similar mechanisms may also operate in the assembly of extracellular matrices in vivo.

Download Full-text

Computational staining of pathology images to study tumor microenvironment in lung cancer

10.1101/630749 ◽

2019 ◽

Author(s):

Shidan Wang ◽

Ruichen Rong ◽

Donghan M. Yang ◽

Ling Cai ◽

Lin Yang ◽

...

Keyword(s):

Gene Expression ◽

Tumor Microenvironment ◽

Spatial Organization ◽

Risk Group ◽

Biological Pathways ◽

The Cancer Genome Atlas ◽

Analysis Tool ◽

Cell Nuclei ◽

Tumor Tissues ◽

Different Types

ABSTRACTThe spatial organization of different types of cells in tumor tissues reveals important information about the tumor microenvironment (TME). In order to facilitate the study of cellular spatial organization and interactions, we developed a comprehensive nuclei segmentation and classification tool to characterize the TME from standard Hematoxylin and Eosin (H&E)-stained pathology images. This tool can computationally “stain” different types of cell nuclei in H&E pathology images to facilitate pathologists in analyzing the TME.A Mask Regional-Convolutional Neural Network (Mask-RCNN) model was developed to segment the nuclei of tumor, stromal, lymphocyte, macrophage, karyorrhexis and red blood cells in lung adenocarcinoma (ADC). Using this tool, we identified and classified cell nuclei and extracted 48 cell spatial organization-related features that characterize the TME. Using these features, we developed a prognostic model from the National Lung Screening Trial dataset, and independently validated the model in The Cancer Genome Atlas (TCGA) lung ADC dataset, in which the predicted high-risk group showed significantly worse survival than the low-risk group (pv= 0.001), with a hazard ratio of 2.23 [1.37-3.65] after adjusting for clinical variables. Furthermore, the image-derived TME features were significantly correlated with the gene expression of biological pathways. For example, transcription activation of both the T-cell receptor (TCR) and Programmed cell death protein 1 (PD1) pathways was positively correlated with the density of detected lymphocytes in tumor tissues, while expression of the extracellular matrix organization pathway was positively correlated with the density of stromal cells.This study developed a deep learning-based analysis tool to dissect the TME from tumor tissue images. Using this tool, we demonstrated that the spatial organization of different cell types is predictive of patient survival and associated with the gene expression of biological pathways. Although developed from the pathology images of lung ADC, this model can be adapted into other types of cancers.

Download Full-text

Spatial Organization and Correlations of Cell Nuclei in Brain Tumors

PLoS ONE ◽

10.1371/journal.pone.0027323 ◽

2011 ◽

Vol 6 (11) ◽

pp. e27323 ◽

Cited By ~ 22

Author(s):

Yang Jiao ◽

Hal Berman ◽

Tim-Rasmus Kiehl ◽

Salvatore Torquato

Keyword(s):

Brain Tumors ◽

Spatial Organization ◽

Cell Nuclei

Download Full-text

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence

10.1101/540146 ◽

2019 ◽

Cited By ~ 2

Author(s):

Konstantinos Sofiadis ◽

Milos Nikolic ◽

Yulia Kargapolova ◽

Natasa Josipovic ◽

Anne Zirkel ◽

...

Keyword(s):

Cell Cycle Progression ◽

Spatial Organization ◽

Rna Binding ◽

Theory Approach ◽

Cell Nuclei ◽

Hmgb1 Protein ◽

Physiological Importance ◽

Genome Wide ◽

Chromatin Folding ◽

Bona Fide

AbstractSpatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is however disturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from senescent cell nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin or about its roles in the nucleus. To address this, we mapped HMGB1 binding genome-wide in different primary cells using a tailored protocol. We integrated ChIP-seq and Hi-C data with a graph theory approach to uncover HMGB1 demarcation of a subset of topologically-associating domains (TADs) that harbor genes required for paracrine senescence. Moreover, using sCLIP, knock-down and overexpression experiments, we now show that HMGB1 is abona fideRNA-binding protein (RBP) bound to senescence-relevant mRNAs and affecting splicing. HMGB1 also has an interactome rich in RBPs, many of which are implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and concertedly regulate the availability of SASP-relevant transcripts. Our findings highlight a broader than hitherto assumed role for HMGB1. It coordinates chromatin folding and RNA homeostasis as part of a feedforward loop controlling both cell-autonomous and paracrine senescence inside and outside of cells.

Download Full-text

Assessment of Directions and Opportunities in Current and Future Materials Education

MRS Bulletin ◽

10.1557/s0883769400067749 ◽

1987 ◽

Vol 12 (4) ◽

pp. 24-27

Author(s):

I.M. Bernstein

Keyword(s):

Chemical Engineering ◽

Materials Science ◽

National Research Council ◽

Science And Engineering ◽

Future Directions ◽

New Directions ◽

Materials Science And Engineering ◽

Unified View ◽

The University ◽

Comprehensive Study

There is considerable excitement and some turmoil in undergraduate and graduate education in the broad field of materials, as well as in its subfields of metallurgy, ceramics, and polymers. While the reasons are many, the underlying driver is the growth in the visibility and diversity of a young field evolving rapidly into a true discipline, much like chemical engineering and biology from their early roots mainly in chemistry.The University Materials Council (UMC), the group representing accredited materials departments has had a longstanding, obvious interest in education and has been actively involved in assessing current and future directions. More recently, a comprehensive study under the auspices of the National Research Council (the Materials Science and Engineering Study), has been undertaken to develop a unified view of recent progress and new directions in materials science and engineering (MSE), and to assess future opportunities and needs. As part of this ambitious endeavor, a panel on education (Panel 5) was established with the following charges:• To investigate and document existing human resources in MSE;• To identify future directions of education in MSE, including education in and out of materials departments;• To identify needs and opportunities for increasing interdisciplinarity in MSE; and• To identify needs and opportunities in lifelong education.

Download Full-text

Detection and Spatiotemporal analysis of in-vitro 3D migratory Triple-Negative Breast cancer cells

10.1101/2021.07.29.454312 ◽

2021 ◽

Author(s):

Nikolaos M Dimitriou ◽

Salvador Flores-Torres ◽

Joseph Matthew Kinsella ◽

Georgios D Mitsis

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Triple Negative Breast Cancer ◽

Spatial Organization ◽

Triple Negative ◽

Migration And Invasion ◽

Great Promise ◽

Cell Nuclei ◽

Wide Range

The invasion of cancer cells into the surrounding tissues is one of the hallmarks of cancer. However, a precise quantitative understanding of the spatiotemporal patterns of cancer cell migration and invasion still remains elusive. A promising approach to investigate these patterns are 3D cell cultures, which provide more realistic models of cancer growth compared to conventional 2D monolayers. Quantifying the spatial distribution of cells in these 3D cultures yields great promise for understanding the spatiotemporal progression of cancer. In the present study, we present an image processing and segmentation pipeline for the detection of 3D GFP-fluorescent Triple-Negative Breast Cancer cell nuclei, and we perform quantitative analysis of the formed spatial patterns and their temporal evolution. The performance of the proposed pipeline was evaluated using experimental 3D cell culture data, and was found to be comparable to manual segmentation, outperforming four alternative automated methods. The spatiotemporal statistical analysis of the detected distributions of nuclei revealed transient, non-random spatial distributions that consisted of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. Overall, the implementation of the proposed framework revealed the spatial organization of cellular nuclei with improved accuracy, providing insights into the 3 dimensional inter-cellular organization and its progression through time.

Download Full-text

Locus-specific gene repositioning in prostate cancer

Molecular Biology of the Cell ◽

10.1091/mbc.e15-05-0280 ◽

2016 ◽

Vol 27 (2) ◽

pp. 236-246 ◽

Cited By ~ 14

Author(s):

Marc Leshner ◽

Michelle Devine ◽

Gregory W. Roloff ◽

Lawrence D. True ◽

Tom Misteli ◽

...

Keyword(s):

Prostate Cancer ◽

Normal Tissue ◽

Spatial Organization ◽

Human Prostate ◽

Specific Gene ◽

Pathological Changes ◽

Cell Nuclei ◽

Prostate Hyperplasia ◽

Interphase Cell ◽

Prostate Disease

Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease.

Download Full-text

ЛАНДШАФТНАЯ ОРГАНИЗАЦИЯ БЕРЕГОВОЙ ГЕОСТРУКТУРЫ ОСТРОВА ШКОТА (ЗАЛИВ ПЕТРА ВЕЛИКОГО)

Geosistemy vostochnyh raionov Rossii: osobennosti ih struktur i prostranstvennogo razvitiia ◽

10.35735/tig.2019.65.23.006 ◽

2019 ◽

Author(s):

K.S. Ganzei ◽

V.V. Zharikov ◽

N.F. Pshenichnikova ◽

A.M. Lebedev ◽

A.G. Kiselyova ◽

...

Keyword(s):

Spatial Organization ◽

Peter The Great Bay ◽

Spatial Arrangement ◽

Water Area ◽

Marine Spatial Planning ◽

Landscape Approach ◽

Important Condition ◽

Statistical Comparison ◽

Peter The Great ◽

Comprehensive Study

Важнейшим условием достижения устойчивого развития прибрежноморского природопользования в заливе Петра Великого системы является морское пространственное планирование. Основой для этого является информация о природных комплексах территории и акватории, полученная на основе ландшафтного подхода. Ключевым районом для изучения пространственной организации ландшафтов прибрежных геоструктур стала территория острова Шкота и его подводных склонов. Для наземных ландшафтов было описано 49 наблюдательных пунктов, 4 профиля были заложены для подводных ландшафтов описано 64 наблюдательных пункта, проложено 18 профилей. Выделено 22 вида ландшафтов, из них 16 наземных, 6 подводных. Берега острова сформированы преобладанием абразивноденудационного и абразивного типов. В результате всестороннего изучения показаны особенности пространственной организации воздушных и водных природных комплексов. Особенностью исследуемой территории является экспозиция дифференциации ландшафтов между юговосточной и северозападной частями острова, обусловленная муссонной природой климата. Результаты полевых и картографических работ послужили основой для выбора зон интенсивного, умеренного и ослабленного взаимодействия наземных и подводных ландшафтов. Пространственное расположение зон взаимодействия четко иллюстрируется значительными различиями экспозиции. Результаты статистического сравнения ландшафтов суши и мелководья, окружающего остров, на основе картометрических характеристик указывают на неоднородность геоструктуры острова, обусловленную, прежде всего, сочетанием ландшафтообразующих факторов. The most important condition for achieving sustainable development of coastalmarine environmental management in Peter the Great Bay is marine spatial planning. The basis for this is information about the natural complexes of the territory and water area, obtained based on the landscape approach. The main area for studying the spatial organization of landscapes of coastal geostructures was the territory of the island of Shkota and its underwater slopes. For terrestrial landscapes, 49 observation points were described, 4 profiles were laid 64 observation points were described for underwater landscapes, 18 profiles were laid. 22 species of landscapes have been identified, of which 16 are terrestrial, 6 are underwater. The shores of the island are formed by the predominance of abrasivedenudation and abrasive types. Because of a comprehensive study, features of the spatial organization of air and aquatic natural complexes are shown. A special feature of the study area is the exposure of the differentiation of landscapes between the southeastern and northwestern parts of the island, due to the monsoon nature of the climate. The results of field and cartographic works served as the basis for selecting areas of intense, moderate and weakened interaction of land and underwater landscapes. The spatial arrangement of the interaction zones is clearly illustrated by significant differences in exposure. The results of a statistical comparison of the land and shallow water landscapes surrounding the island, based on the cartometric characteristics, indicate the heterogeneity of the islands geostructure, primarily due to the combination of landscapeforming factors.

Download Full-text