Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of a human airway epithelial cell subpopulation with altered biophysical, molecular, and metastatic properties

ABSTRACT: Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant pulmonary epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of unselected cells. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8-weeks post-selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short term assays and enhanced outgrowth of premalignant lesions in longer term assays, thus overcoming important aspects of “metastatic inefficiency.” Overall, our findings indicate that among premalignant pulmonary epithelial cells, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100527 | GEO | 2017/06/28

SECONDARY ACCESSION(S): PRJNA392037

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNAseq of rabbit lungs infected with Mycobacterium tuberculosis as single cells or aggregates

Project description:The virulence of Mycobacterium tuberculosis (Mtb), either as mostly aggregates or single cells (Mtb-SC), was compared using a rabbit model of pulmonary infection. Our hypothesis is that aggregation contributes to enhanced virulence of Mtb. Rabbit lung transcriptome was analyzed by RNAseq to identify differentially regulated gene networks and pathways between Mtb-AG and Mtb-SC infection of rabbit lungs soon after seeding of the bacteria (24 hours post-inoculation).

2021-09-22 | GSE176139 | GEO

Snail-dependent epithelial splicing regulatory protein 1 (ESRP1) silencing drives malignant transformation of human pulmonary epithelial cells [miRNA]

Project description:The significance of epithelial-to-mesenchymal transition (EMT)-inducing transcription factors in the onset of non-small cell lung cancer has not been resolved. Here, we report increased Snail expression in pulmonary premalignant lesions relative to histologically normal-appearing pulmonary epithelium. Utilizing immortalized human pulmonary epithelial cells and isogenic derivatives, we document Snail-dependent anchorage-independent growth of the epithelial cells in vitro, as well as transformation, primary tumor growth, and metastatic behavior in vivo. Epithelial splicing regulatory protein 1 (ESRP1) tumor suppressor silencing was a requirement for Snail-driven transformation in vivo, and we identified ESRP1 loss in Snail-expressing pulmonary premalignant lesions in situ. Snail drives these and other carcinogenic signaling programs in an ALDH+CD44+CD24- pulmonary stem cell subset in which ESRP1 and stemness-repressing micro-RNAs are inhibited.

2017-12-16 | GSE108136 | GEO

Snail-dependent epithelial splicing regulatory protein 1 (ESRP1) silencing drives malignant transformation of human pulmonary epithelial cells [mRNA]

2017-12-16 | GSE108135 | GEO

miRNA expression in high migratory cells

Project description:microRNAs are small non-coding RNAs, which promote either mRNAs degradation or block their translation through binding to partially complementary sequences of their target mRNAs. We have previously isolated a subpopulation with accelerated baseline motility (MG cells) or an immotile one (non-MG cells) from a colon cancer cell line (HCT116). In this study, using these subpopulations, we identified miRNAs, which were involved in acquisition of a cell migratory phenotype.

2020-02-27 | GSE141240 | GEO

Mechanics of a multilayer epithelium instruct tumor architecture and function [adult]

Project description:Loss of normal tissue architecture is a hallmark of oncogenic transformation. Mechanical forces sculpt tissue architectures during morphogenesis. However, their origins and consequences during tumorigenesis remain elusive. In skin, premalignant basal cell carcinomas (BCCs) form ‘buds’, while invasive squamous cell carcinomas (SCC) initiate as ‘folds’. Using computational modeling, genetic manipulations and biophysical measurements, we identify the biophysical underpinnings and biological consequences of these tumor architectures. Cell proliferation and actomyosin contractility dominate tissue architectures in monolayer, but not multilayer epithelia. In stratified epidermis, softening and enhanced remodeling of the basement membrane (BM) promote tumor budding, while BM stiffening promotes folding. We show that additional key forces stem from progenitor cell stratification and differentiation Tumor-specific suprabasal stiffness gradients are generated as oncogenic lesions progress toward malignancy, which we computationally predict alter extensile tensions on the tumor BM. The pathophysiologic ramifications of this prediction are profound. Genetically decreasing BM stiffness elevates BM tensions in silico and potentiates invasive SCC progression in vivo. Our findings suggest that mechanical forces, exerted from above and below progenitors of multilayered epithelia, are integrally linked and function to shape premalignant tumor architectures and influence tumor progression.

2020-07-01 | GSE152487 | GEO

Mechanics of a multilayer epithelium instruct tumor architecture and function [E15]

2020-07-01 | GSE152486 | GEO

Lung dendritic cells migrate to the spleen to prime long-lived memory CD8+ T cell precursors after influenza virus infection

Project description:CD8+ T cell responses to pulmonary challenges are primed by lung-migratory dendritic cells (mDCs), which capture antigens in the lung and migrate to the lung-draining mediastinal lymph node (med-LNs) to activate T cells. Notably, the lung and the spleen are not connected by the lymphatic vasculature. Thus, the current paradigm suggests that the med-LN is the only site for T cell priming to viruses that are restricted to the respiratory tract. Our results challenge this “LN-centric” paradigm. Using an influenza virus infection, we show here that lung-mDCs egress the med-LN and traffic to the spleen, where they prime influenza-specific CD8+ T cells. Importantly, CD8+ T cells primed in the spleen are transcriptionally different and have enhanced ability to differentiate into long-lived memory cells compared to med-LN-primed counterparts. Thus, our data reveal a previously ignored lung-mDC trafficking pathway that connects the lung with the spleen and has profound immunological implications.

2021-07-16 | GSE179995 | GEO

RNA-seq time series of lung epithelial and lung mesenchymal cells in a novel co-culture model of lung fibrosis

Project description:The interaction of lung epithelial and lung mesenchymal cells (fibroblasts) was investigated in a novel co-culture model of human pulmonary fibrosis. Remarkably, co-culturing both cell types induced cell-type-specific responses, including fibroblast-to-myofibroblast differentiation and epithelial-to-mesenchymal transition (EMT), which were fully dependent on direct epithelial / fibroblast contact. Primary normal human lung fibroblasts (NHLF) and normal human bronchiolar epithelial cells (NHBE) were fluorescently labelled prior to seeding, then grown either as mono or co-cultures and collected in triplicates for mRNA-seq at the start (T=0h) and after 3h and 18h. Each harvested cell culture was FACS sorted into individual NHLF and NHBE cell populations, which were then then lysed and sequenced.

2022-10-03 | E-MTAB-11832 | biostudies-arrayexpress

Multimodal decoding of human liver regeneration [st_human]

Project description:Using snRNA-seq combined with spatial profiling of healthy and ALF explant human livers, we uncover a novel migratory hepatocyte subpopulation. We discover a corollary subpopulation in a mouse model of APAP-induced liver regeration, and demonstrate that this subpopulation meidates wound closure following liver injury.

2023-02-01 | GSE223559 | GEO

Multimodal decoding of human liver regeneration [snrna_mouse]

2023-02-01 | GSE223558 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data