Dataset Information

Chromosome conformation and gene expression patterns differ profoundly in human fibroblasts grown in spheroids versus monolayers.

ABSTRACT: Human cells derived for in vitro cultures are conventionally grown as adherent monolayers (2D) which do not resemble natural 3 dimensional (3D) tissue architecture. We examined genome structure with chromosome conformation capture (Hi-C) and gene expression with RNA-seq in fibroblasts derived from human foreskin grown in 2D and 3D conditions. Our combined analysis of Hi-C and RNA-seq data shows a large number of differentially expressed genes between 2D and 3D cells, and these changes are localized in genomic regions that displayed structural changes. We also find a trend of expression in a subset of skin-specific genes in fibroblast cells grown in 3D that resembles those in native tissue.

SUBMITTER: Chen H

PROVIDER: S-EPMC5597289 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chromosome conformation and gene expression patterns differ profoundly in human fibroblasts grown in spheroids versus monolayers.

Chen Haiming H Seaman Laura L Liu Sijia S Ried Thomas T Rajapakse Indika I

Nucleus (Austin, Tex.) 20170127 4

Human cells derived for in vitro cultures are conventionally grown as adherent monolayers (2D) which do not resemble natural 3 dimensional (3D) tissue architecture. We examined genome structure with chromosome conformation capture (Hi-C) and gene expression with RNA-seq in fibroblasts derived from human foreskin grown in 2D and 3D conditions. Our combined analysis of Hi-C and RNA-seq data shows a large number of differentially expressed genes between 2D and 3D cells, and these changes are locali ...[more]

PMID: 28129029

Similar Datasets

Project description:BackgroundAlthough coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms.MethodsUsing ex vivo cell models, we sought to analyze SARS-CoV-2 interactions with kidney tubular cells and assess direct tubular injury. These models comprised primary human kidney epithelial cells (derived from nephrectomies) and grown as either proliferating monolayers or quiescent three-dimensional kidney spheroids.ResultsWe demonstrated that viral entry molecules and high baseline levels of type 1 IFN-related molecules were present in monolayers and kidney spheroids. Although both models support viral infection and replication, they did not exhibit a cytopathic effect and cell death, outcomes that were strongly present in SARS-CoV-2-infected controls (African green monkey kidney clone E6 [Vero E6] cultures). A comparison of monolayer and spheroid cultures demonstrated higher infectivity and replication of SARS-CoV-2 in actively proliferating monolayers, although the spheroid cultures exhibited high er levels of ACE2. Monolayers exhibited elevation of some tubular injury molecules-including molecules related to fibrosis (COL1A1 and STAT6) and dedifferentiation (SNAI2)-and a loss of cell identity, evident by reduction in megalin (LRP2). The three-dimensional spheroids were less prone to such injury.ConclusionsSARS-CoV-2 can infect kidney cells without a cytopathic effect. AKI-induced cellular proliferation may potentially intensify infectivity and tubular damage by SARS-CoV-2, suggesting that early intervention in AKI is warranted to help minimize kidney infection.

Dataset Information

Chromosome conformation and gene expression patterns differ profoundly in human fibroblasts grown in spheroids versus monolayers.

Publications

Chromosome conformation and gene expression patterns differ profoundly in human fibroblasts grown in spheroids versus monolayers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets