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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

ABSTRACT: To identify regions of open chromatin ATAC-seq was carried out in Blood outgrowth endothelial cells (BOECs) and NCI-H441 Epithelial cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE175789 | GEO | 2021/08/13

REPOSITORIES: GEO

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Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus.

Project description:The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial-mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target.

| S-EPMC7611960 | biostudies-literature

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

Project description:To identify a causative variant and effector gene responsible for a 2-fold increased risk of severe COVID-19, a multi-omics platform was deployed. A combination of ATAC-seq, ChIP-seq, Micro Capture-C and NuTi Capture-C were used to characterize a range of cell types, including epithelial, fibroblast, endothelial, immune and erythroid cells.

2021-08-13 | GSE175791 | GEO

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (MCC)

Project description:To identify regulatory interactions in erythroid, fibroblast and endothelial cells Micro Caputre-C was carried outfrom the promoters of active genes as well as the rs17713054 containing enhancer.

2021-08-31 | GSE175790 | GEO

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ChIP-seq)

Project description:To identify regulation by the CEBPB transcription factor in epithelial, fibroblast and endothelial cells ChIP-seq was carried out for both the transcription factor and marks of active transcription (H3K27ac).

2021-08-13 | GSE175788 | GEO

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

Project description:Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus

| PRJNA733663 | ENA

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (MCC)

Project description:Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (MCC)

| PRJNA733668 | ENA

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ChIP-seq)

Project description:Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ChIP-seq)

| PRJNA733666 | ENA

Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

Project description:Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus (ATAC-seq)

| PRJNA733669 | ENA

Replication of LZTFL1 Gene Region as a Susceptibility Locus for COVID-19 in Latvian Population.

Project description: Not available

| S-EPMC8526276 | biostudies-literature

Hyaluronidase-1 impairs endothelial barrier in a subtype of age-related macular degeneration

Project description:Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Here, we cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls. When BOECs were exposed to heterogeneous flow, single-cell analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of endothelial glycocalyx. Hyaluronidase-1 was correspondingly detected in PCV patient vitreous humor and plasma samples. Notably, knockdown of hyaluronidase-1 in PCV BOECs modulated their abnormal cell migration and barrier permeability due to glycocalyx impairment. Therefore, hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

2022-01-20 | GSE179631 | GEO

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