Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TCF21high pericyte subpopulation promotes cancer metastasis by remodeling perivascular matrix

ABSTRACT: The role of perivascular cell heterogeneity in tumor metastasis remains unknown. Here, we dissected the heterogeneity of perivascular cells by single-cell RNA sequencing and defined 13 subpopulations of pericytes within human colorectal cancers (CRC). Among them, an extracellular matrix (ECM)-rich subpopulation of TCF21high tumor pericytes (TPCs) was identified, which highly correlated with metastatic potentials in human CRC patients. Pericyte-specific conditional deletion of Tcf21 in mice mitigated CRC metastasis by decreasing perivascular ECM resmodeling, maintaining the integrity of the basement membrane, and reducing circulating cancer cells. Conversely, co-injection of CRC cells with TCF21high TPCs markedly promoted metastasis. Mechanistically, high expression of TCF21 in TPCs altered ECM stiffness, collagen deposition/rearrangement, and basement membrane degradation, which collectively instigated tumor cell intravasation and metastasis. Compelling experimental evidence showed that the loss of integrin α5 activated the FAK/PI3K/AKT axis, impaired DNA hypermethylation of TCF21, leading to high expression of TCF21 in TPCs. Our data provide new mechanistic insights into functions of a specific subpopulation of perivascular cells in promoting cancer metastasis and therapeutic targeting of metastasis-promoting TPCs may provide a new paradigm for cancer therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199726 | GEO | 2023/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Vascular organoids differentiation from human induced pluripotent stem cells (iPSC)

Project description:We have established a vascular organoid culture system with self-assembled endothelial networks that are covered by a basement membrane and pericytes. CD31+ endothelial cells, and CD140b positive pericytes were FACS sorted and RNA-seq was performed.

2020-01-01 | GSE108726 | GEO

Endothelial cells derived from iPSC in response to diabetic medium

Project description:Diabetes is prevalent worldwide and associated with severe health complications, including blood vessel damage that leads to cardiovascular disease and death. We report the development of 3D blood vessel organoids from human embryonic and induced pluripotent stem cells. These human blood vessel organoids contain endothelium, perivascular pericytes, and basal membranes, and self-assemble into lumenized interconnected capillary networks. We treat these vascular organoids with hyperglycemia and inflammatory cytokines in vitro, which leads to basement membrane thickening, a structural hallmark of diabetic patient. To compare differential gene expression we performed RNAseq on endothelial cells, derived from control (NG) or diabetic (DI) vascular organoids.

2018-08-01 | GSE89475 | GEO

A subpopulation of Periostin-expressing fibroblasts is required for cardiac muscle and neuronal maturation after birth

Project description:During the postnatal period in mammals, the cardiac muscle transitions from hyperplasic to hypertrophic growth, the extracellular matrix (ECM) undergoes remodeling, and the heart loses regenerative capacity. While ECM maturation and crosstalk between cardiac fibroblasts (CFs) and cardiomyocytes (CM) have been implicated in neonatal heart development, not much is known about specialized fibroblast heterogeneity and functions in the early postnatal period. In order to better understand CF functions in heart maturation and postnatal cardiomyocyte cell cycle arrest, we have performed gene expression profiling and ablation of postnatal CF subpopulations. Fibroblast lineages expressing Tcf21 or Periostin were traced in transgenic GFP reporter mice and their biological functions and transitions during the postnatal period were examined in sorted cells using RNAseq. A subpopulation of highly proliferative Periostin (Postn)+ CFs was found from postnatal day (P)1 to P11 but was not detected at P30. This population was less abundant and transcriptionally different from Tcf21+ resident CFs, which persist in the mature heart. The Postn+ subpopulation preferentially expresses genes related to cell proliferation and neuronal development, while Tcf21+ CFs differentially express genes related to ECM maturation at P7 and immune crosstalk at P30. Ablation of the Postn+ CFs from P0 to P6 led to altered cardiac sympathetic nerve patterning and a reduction in CM binucleation, maturation, and hypertrophic growth. Thus, postnatal CFs are heterogeneous and include a transient proliferative Postn+ subpopulation required for cardiac nerve development and cardiomyocyte maturation soon after birth.

2020-08-05 | GSE144587 | GEO

CD44+ Lung Cancer Stem Cell-derived Vascular Pericytes Cause Brain Metastases through GPR124-mediated Trans-endothelial Migration [II]

Project description:Brain metastasis of lung cancer causes high mortality, but the exact mechanisms underlying the metastasis remain unclear. Here we report that vascular pericytes derived from CD44+ lung cancer stem cells (CSCs) in lung adenocarcinoma (ADC) potently cause brain metastases through GPR124-mediated trans-endothelial migration (TEM). CD44+ CSCs in the perivascular niche generate the majority of vascular pericytes in lung ADC. CSC-derived pericyte-like cells (Cd-pericytes) exhibit remarkable TEM capacity to effectively intravasate into vessel lumina, survive in the circulation, extravasate into the brain parenchyma, and then de-differentiate into tumorigenic CSCs to form metastases. Moreover, Cd-pericytes uniquely express GPR124, a G-protein-coupled receptor. GPR124 mediates through Wnt7-β-Catenin activation to enhance TEM capacity of Cd-pericytes for intravasation and extravasation, two critical steps during tumor metastasis. Furthermore, selective disruption of Cd-pericytes, GPR124 or Wnt7-β-Catenin signaling markedly reduced brain and liver metastases of lung ADC. Our findings uncover an unappreciated cellular and molecular paradigm driving tumor metastasis.

2023-07-23 | GSE237317 | GEO

CD44+ Lung Cancer Stem Cell-derived Vascular Pericytes Cause Brain Metastases through GPR124-mediated Trans-endothelial Migration [I]

2023-07-23 | GSE237316 | GEO

RNA-seq of human cerebromicrovascular endothelial cell line hCMEC/D3 or primary human brain vascular pericytes stimulated with TNF, or S. pneumoniae, in monoculture or in coculture, or stimulated with conditioned media from monocyte-derived macrophages (MDM) stimulated with S. pneumoniae, all compared to unstimulated controls

Project description:The interplay of cerebromicrovascular endothelial cells, pericytes and perivascular macrophages is central to the recruitment of neutrophils across the blood-brain barrier into the brain, and therefore to the CNS inflammatory response. This experiment examined the endothelial response to direct stimulation in the presence or absence of pericytes to explore the effect of co-culture on the endothelial inflammatory response. It also assessed the endothelial response to signalling by monocyte-derived macrophages, modelling perivascular macrophages, the only canonical innate immune cell found within the perivascular space.

2022-08-31 | E-MTAB-11129 | biostudies-arrayexpress

TCF21high pericyte subpopulation promotes cancer metastasis by remodeling perivascular matrix

Project description:TCF21high pericyte subpopulation promotes cancer metastasis by remodeling perivascular matrix

| PRJNA821245 | ENA

ECM-dependent gene expression in normal and tumor-derived mammary organoids

Project description:A critical step in metastasis is cancer cell dissemination. Dissemination and metastasis are associated with specific genetic changes and changes in extracellular matrix (ECM), but how these changes interact to enable dissemination remains unclear. Here we tested the importance of ECM to dissemination in both normal and malignant mammary epithelium. By time-lapse imaging, we observed collective invasion and dissemination directly in 3D culture. Our results reveal that the pattern of epithelial migration and local dissemination are constrained by the local ECM microenvironment. To identify RNA expression changes that could regulate these changes in cell behavior, we conducted whole genome RNA expression profiling from normal and malignant mammary epithelium in 3D culture. We collected RNA from normal and malignant epithelium during active growth at 4 days in culture in either Matrigel or collagen I. We hybridized the resulting RNA to Agilent single color microarrays with a minimum of three biologically independent microarray replicates per condition. We observed significant gene expression differences between normal and malignant epithelium, even when cultured in the same ECM. In contrast, the ECM microenvironment had a relatively small impact on RNA expression, despite its large effects on migratory strategy and local dissemination. Gene expression was measured in normal and malignant mammary epithelial fragments cultured in one of two 3D matrices (laminin-rich basement membrane gel or collagen I) and collected at day 4, which we observed to have peak invasion and dissemination. At least three independent experiments were performed at each time using different mice for each experiment.

2012-08-16 | E-GEOD-39173 | biostudies-arrayexpress

Data in support of Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier

Project description:The aim of the present study was to analyze four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). The mBCECs and pericytes were isolated from brains of adult C57BL/6 mice, and glial cells (mainly astrocytes and microglia) were prepared from cerebral cortices of newborn C57BL/6 mice. The mBCECs were grown as mono-culture, in co-culture with pericytes or mixed glial cells, or as a triple-culture with both pericytes and mixed glial cells.

2016-08-03 | PXD003981 | Pride

Gene expression analysis of human adipose-derived stem cells.

Project description:Transcriptional activity was identified in all categories of genes expressed by ADSC, including collagens, ECM and basement membrane constituents, adhesion molecules involved in cell-cell and cell-matrix interactions, and proteases involved in degradation of the ECM and their inhibitors. Importantly, it was observed that ADSC synthesize and secrete all three collagen VI chains, suggesting suitability of ADSC for collagen VI congenital muscular dytrophy treatment. We developed a procedure for isolation of human stem cells from adipose layer of neonatal foreskin skin. The adipose-derived stem cells (ADSC) were examined for expression of extracellular matrix (ECM) and related genes using gene expression array analysis.

2013-09-21 | E-GEOD-51030 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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