HCA Data Explorer

Stress-induced RNA–chromatin interactions promote endothelial dysfunction

Updated November 16, 2021

Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.

Sheng ZhongUniversity of California San Diegoszhong@eng.ucsd.edu
Zhen Bouman ChenBeckman Research Institute, City of Hopezhenchen@coh.org

Stress-induced RNA-chromatin interactions promote endothelial dysfunction

Riccardo Calandrelli1
Lixia Xu2
Yingjun Luo2
Weixin Wu1
Xiaochen Fan1
Tri Nguyen1
Chien-Ju Chen1
Kiran Sriram2
Xiaofang Tang2
Andrew B. Burns2
Rama Natarajan2
Sheng Zhong1
Zhen Bouman Chen2
Lattice Data Coordination (External Curator)3
1University of California San Diego
2Beckman Research Institute, City of Hope
3Stanford University
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/87d52a86-bdc7-440c-b84d-170f7dc346d9

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://cellxgene.cziscience.com/collections/db468083-041c-41ca-8f6f-bf991a070adf
None

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Analysis Portals

CZ CELLxGENECZ CELLxGENE

Project Label

Stress-inducedRNA–chromatininteractionspromoteendo

Species

Homo sapiens

Sample Type

2 sample types

Anatomical Entity

arterial blood vessel

Organ Part

mesenteric artery

Selected Cell Types

endothelial cell of artery

Model Organ

Unspecified

Disease Status (Specimen)

Unspecified

Disease Status (Donor)

5 disease statuses

Development Stage

2 development stages

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

MergeOptimusLooms_v1.0.0, Optimus_v5.1.2

File Format

3 file formats

Cell Count Estimate

Unspecified

Donor Count

5
bam10 file(s)fastq40 file(s)loom11 file(s)