Epithelial Cells in 2D and 3D Cultures Exhibit Large Differences in Higher-order Genomic Interactions  

作　　者：Xin Liu Qiu Sun Qi Wang Chuansheng Hu Xuecheng Chen Hua Li Daniel M.Czajkowsky Zhifeng Shao 

机构地区：[1]State Key Laboratory for Oncogenes and Bio-ID Center,School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China [3]Translational Medical Center for Stem Cell Therapy&Institute for Regenerative Medicine,Shanghai East Hospital,School of Life Science and Technology,Shanghai Key Laboratory of Signaling and Disease Research,Tongji University,Shanghai 200092,China

出　　处：《Genomics, Proteomics & Bioinformatics》2022年第1期101-109,共9页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the grants from the National Key R&D Program of China(Grant No.2018YFC1003500);the National Natural Science Foundation of China(Grant Nos.11374207,31501054,31670722,31971151,81627801,and 31900430);the China Postdoctoral Science Foundation(Grant No.2018M640419);the generous support from Nikon Instruments(Shanghai)Co.,Ltd。

摘　　要：Recent studies have characterized the genomic structures of many eukaryotic cells,often focusing on their relation to gene expression.However,these studies have largely investigated cells grown in 2D cultures,although the transcriptomes of 3D-cultured cells are generally closer to their in vivo phenotypes.To examine the effects of spatial constraints on chromosome conformation,we investigated the genomic architecture of mouse hepatocytes grown in 2D and 3D cultures using in situ Hi-C.Our results reveal significant differences in higher-order genomic interactions,notably in compartment identity and strength as well as in topologically associating domain(TAD)-TAD interactions,but only minor differences are found at the TAD level.Our RNA-seq analysis reveals up-regulated expression of genes involved in physiological hepatocyte functions in the 3D-cultured cells.These genes are associated with a subset of structural changes,suggesting that differences in genomic structure are critically important for transcriptional regulation.However,there are also many structural differences that are not directly associated with changes in gene expression,whose cause remains to be determined.Overall,our results indicate that growth in 3D significantly alters higher-order genomic interactions,which may be consequential for a subset of genes that are important for the physiological functioning of the cell.

关 键 词：3D culture In situ Hi-C Chromosome conformation COMPARTMENT TAD 

分 类 号：Q343[生物学—遗传学]