title: 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.
authors.affiliation: a Department of Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Haiming
authors.initials: H
authors.lastname: Chen
authors.affiliation: a Department of Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Seaman
authors.affiliation: a Department of Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Sijia
authors.initials: S
authors.lastname: Liu
authors.affiliation: b Section of Cancer Genomics, Center for Cancer Research , National Cancer Institute , Bethesda , MD , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.affiliation: a Department of Computational Medicine and Bioinformatics , University of Michigan , Ann Arbor , MI , USA.|c Department of Mathematics , University of Michigan , Ann Arbor , MI , USA.
authors.forename: Indika
authors.initials: I
authors.lastname: Rajapakse
mesh_terms: D018929:Cell Culture Techniques; D002875:Chromosomes / Q000737:chemistry*; D005347:Fibroblasts / Q000737:chemistry* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008968:Molecular Conformation; D060888:Real-Time Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000502:physiology
keywords: Fiedler number; Gene Ontology; form; function; nucleome; topologically associating domain