scholarly journals A LINCS microenvironment perturbation resource for integrative assessment of ligand-mediated molecular and phenotypic responses

2021 ◽  
Author(s):  
Sean M Gross ◽  
Mark A Dane ◽  
Rebecca L Smith ◽  
Kaylyn Devlin ◽  
Ian Mclean ◽  
...  
Keyword(s):  
Mammary Epithelial Cells ◽  
Molecular State ◽  
Mammary Epithelial ◽  
Systematic Assessment ◽  
Extracellular Signals ◽  
Molecular Features ◽  
Integrative Assessment ◽  
A Cell ◽  
Cellular Phenotypes ◽  
Phenotypic Responses

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods (synapse.org/LINCS_MCF10A). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes.

scholarly journals scRNA-seq Reveals A Macrophage Subset That Provides A Splenic Replication Niche For Intracellular Salmonella

2021 ◽  
Author(s):  
Dotan Hoffman ◽  
Yaara Tevet ◽  
Gili Rosenberg ◽  
Leia Vainman ◽  
Aryeh Solomon ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Growth Dynamics ◽  
Systemic Infection ◽  
Mononuclear Phagocytes ◽  
Second Phase ◽  
Molecular Features ◽  
A Cell ◽  
Macrophage Subset ◽  
Cellular Phenotypes ◽  
Classical Monocytes

AbstractInteractions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single cell RNA-seq (scRNA-seq) have identified multiple subsets within the mononuclear population defined by unique molecular features, but the implications to their function during infection is unknown. Here, we applied high resolution kinetic analysis using microscopy, flow cytometry and scRNA-seq to survey the mononuclear niche of intracellular Salmonella Typhimurium (S.Tm) during early systemic infection in mice. We describe an eclipse like growth kinetics in the spleen, with a first phase of bacterial control mediated by tissue resident red pulp macrophages. A second phase involved bacterial growth mediated by intracellular replication within a macrophage population we termed CD9 macrophages, that originate from non-classical monocytes. Nr4a1e2−/− mice, specifically depleted of non-classical monocytes but not other mononuclear cells, are more resistant to S.Tm infection. Our study underscores a cell-type specific host-pathogen interaction that determines early infection growth dynamics and has implications to the infection outcome of the entire organism.

scholarly journals CYFIP2 containing WAVE complexes inhibit cell migration

2020 ◽  
Author(s):  
Anna Polesskaya ◽  
Arthur Boutillon ◽  
Yanan Wang ◽  
Marc Lavielle ◽  
Sophie Vacher ◽  
...  
Keyword(s):  
Cell Migration ◽  
Mammary Epithelial Cells ◽  
Leading Edge ◽  
Good Prognosis ◽  
Mammary Epithelial ◽  
Breast Cancer Patients ◽  
Loss Of Function ◽  
A Cell ◽  
Wave Complex

ABSTRACTBranched actin networks polymerized by the Arp2/3 complex are critical for cell migration. The WAVE complex is the major Arp2/3 activator at the leading edge of migrating cells. However, multiple distinct WAVE complexes can be assembled in a cell, due to the combinatorial complexity of paralogous subunits. When systematically analyzing the contribution of each WAVE complex subunit to the metastasis-free survival of breast cancer patients, we found that overexpression of the CYFIP2 subunit was surprisingly associated with good prognosis. Gain and loss of function experiments in transformed and untransformed mammary epithelial cells revealed that cell migration was always inversely related to CYFIP2 levels. The role of CYFIP2 was systematically opposite to the role of the paralogous subunit CYFIP1 or of the NCKAP1 subunit. The specific CYFIP2 function in inhibiting cell migration was related to its unique ability to down-regulate classical pro-migratory WAVE complexes. The anti-migratory function of CYFIP2 was also revealed in migration of prechordal plate cells during gastrulation of the zebrafish embryo, indicating that the unique function of CYFIP2 is critically important in both physiological and pathophysiological migrations.

C2-ceramide as a cell death inducer in HC11 mouse mammary epithelial cells

2004 ◽  
Vol 203 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Sung Hak Kim ◽  
Sung Chan Kim ◽  
Yoon Jung Kho ◽  
Sung Wook Kwak ◽  
Hong Gu Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
A Cell

Quantitative Model-Based Image Analysis of NuMa Distribution Links Nuclear Organization with Cell Phenotype

2001 ◽  
Vol 7 (S2) ◽  
pp. 578-579
Author(s):  
David W. Knowles ◽  
Sophie A. Lelièvre ◽  
Carlos Ortiz de Solόrzano ◽  
Stephen J. Lockett ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Image Analysis ◽  
Mammary Epithelial Cells ◽  
Nuclear Organization ◽  
Critical Role ◽  
Quantitative Model ◽  
Mammary Epithelial ◽  
Cell Phenotype ◽  
Proliferating Cells ◽  
Mitotic Apparatus ◽  
Model Based

The extracellular matrix (ECM) plays a critical role in directing cell behaviour and morphogenesis by regulating gene expression and nuclear organization. Using non-malignant (S1) human mammary epithelial cells (HMECs), it was previously shown that ECM-induced morphogenesis is accompanied by the redistribution of nuclear mitotic apparatus (NuMA) protein from a diffuse pattern in proliferating cells, to a multi-focal pattern as HMECs growth arrested and completed morphogenesis . A process taking 10 to 14 days.To further investigate the link between NuMA distribution and the growth stage of HMECs, we have investigated the distribution of NuMA in non-malignant S1 cells and their malignant, T4, counter-part using a novel model-based image analysis technique. This technique, based on a multi-scale Gaussian blur analysis (Figure 1), quantifies the size of punctate features in an image. Cells were cultured in the presence and absence of a reconstituted basement membrane (rBM) and imaged in 3D using confocal microscopy, for fluorescently labeled monoclonal antibodies to NuMA (fαNuMA) and fluorescently labeled total DNA.

Sign in / Sign up

Export Citation Format

Share Document