Epithelial Cells in 2D and 3D Cultures Exhibit Large Differences in Higher-order Genomic Interactions.
Epithelial Cells in 2D and 3D Cultures Exhibit Large Differences in Higher-order Genomic Interactions.
复制标题
2D 和 3D 培养物中的上皮细胞在高阶基因组相互作用中表现出巨大差异
DOI：
10.1016/j.gpb.2020.06.017
复制
发表时间：
2022-02
期刊：
影响因子：
--
通讯作者：
Shao Z
中科院分区：
文献类型：
--
作者：
Liu X;Sun Q;Wang Q;Hu C;Chen X;Li H;Czajkowsky DM;Shao Z
最近的研究已经表征了许多真核细胞的基因组结构，通常集中在它们与基因表达的关系上。然而，这些研究在很大程度上研究了在2D培养中生长的细胞，尽管3D培养细胞的转录组通常更接近其体内表型。为了研究空间限制对染色体构象的影响，我们使用原位Hi-C研究了在2D和3D培养中生长的小鼠肝细胞的基因组结构。我们的研究结果揭示了高阶基因组相互作用的显着差异，特别是在车厢的身份和强度，以及在拓扑关联结构域（ESTA）-ESTA的相互作用，但只有微小的差异被发现在ESTA水平。我们的RNA-seq分析揭示了在3D培养的细胞中参与生理肝细胞功能的基因的上调表达。这些基因与结构变化的子集相关，表明基因组结构的差异对转录调控至关重要。然而，也有许多结构差异与基因表达的变化没有直接关系，其原因仍有待确定。总体而言，我们的研究结果表明，3D生长显着改变了高阶基因组相互作用，这可能对细胞生理功能重要的基因子集产生影响。
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 an 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.
登录
查看更多内容
影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.5
作者：
Dekker J;Mirny L
通讯作者：
Mirny L
影响因子：
5.6
作者：
Antoni D;Burckel H;Josset E;Noel G
通讯作者：
Noel G
DOI：
10.1186/1748-7188-9-14
发表时间：
2014
期刊：
Algorithms for molecular biology : AMB
影响因子：
--
作者：
Filippova D;Patro R;Duggal G;Kingsford C
通讯作者：
Kingsford C
DOI：
10.1093/toxsci/kfx289
发表时间：
2018-04-01
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Bell CC;Dankers ACA;Lauschke VM;Sison-Young R;Jenkins R;Rowe C;Goldring CE;Park K;Regan SL;Walker T;Schofield C;Baze A;Foster AJ;Williams DP;van de Ven AWM;Jacobs F;Houdt JV;Lähteenmäki T;Snoeys J;Juhila S;Richert L;Ingelman-Sundberg M
通讯作者：
Ingelman-Sundberg M