Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [ChIP-seq]

ABSTRACT: Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development. Here, we describe a novel enhancer element important for regulating Prox1 expression in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. CRISPR-Cas9 genome editing of this enhancer element revealed that deletion of only 5 nucleotides encompassing the GATA2 binding site has a dramatic impact on lymphatic vascular development; mice homozygous for this deletion die soon after birth exhibiting profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibit reduced levels of genes characteristic of lymphatic endothelial cell identity and acquire characteristics of hemogenic endothelium, including the capacity to generate hematopoietic cells. These data reveal the first transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity and suggest that Prox1 is important for repressing hemogenic cell identity in the lymphatic endothelium.

ORGANISM(S): Homo sapiens

PROVIDER: GSE129632 | GEO | 2022/11/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [RNA-seq]

Project description:Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development. Here, we describe a novel enhancer element important for regulating Prox1 expression in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. CRISPR-Cas9 genome editing of this enhancer element revealed that deletion of only 5 nucleotides encompassing the GATA2 binding site has a dramatic impact on lymphatic vascular development; mice homozygous for this deletion die soon after birth exhibiting profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibit reduced levels of genes characteristic of lymphatic endothelial cell identity and acquire characteristics of hemogenic endothelium, including the capacity to generate hematopoietic cells. These data reveal the first transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity and suggest that Prox1 is important for repressing hemogenic cell identity in the lymphatic endothelium.

2022-11-21 | GSE129633 | GEO

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer (RNA-Seq)

Project description:This study investigates the impact on the transcriptome of lymphatic endotheial cells of a 5bp deletion (GATA2 binding site) in an enhancer element 11kb upstream of the Prox1 gene.

2022-11-21 | GSE184044 | GEO

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer

| PRJNA532344 | ENA

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer

| PRJNA762884 | ENA

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer (Microarray)

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer (Microarray)

| PRJNA762902 | ENA

Glycan analysis of promary human lymphatic endothlial cells (LEX) in their resting and activated states, in normal and tumor tissues

Project description:Trafficking of leukocytes (dendritic cells, memory T cells, neutrophils) and tumor cells through the lymphatic network is a key process in inflammation and immunity and an important mechanism in metastatic spread of human cancers (1-3). Such trafficking involves both communication with and passage across lymphatic endothelium, the distinct endothelium that lines lymphatic vessels within the peripheral tissues and forms the lymphatic sinuses within lymph nodes. However, in comparison with blood vascular endothelium, there is only a rudimentary understanding of the molecular phenotype of lymphatic endothelium, and only a basic knowledge of the glycoconjugates that regulate leukocyte-endothelial and tumor cell-endothelial interactions in the lymphatic compartment. We would anticipate that changes in glycosylation of LEC cell surface proteins following activation might affect important functions associated withy LEC including eg. interactions with leukocytes and/or sequestration of GAG-binding chemokines. We already have shown that ligand binding to the lymphatic endothelial hyaluronan receptor LYVE-1 is reversibly masked by terminal sialation in LEC and that functional regulation of LYVE-1 is likely to be important in inflammation. An advantage of our proposal is that we can routinely isolate primary LEC in relatively large numbers, and have the necessary ethical approval to do so from human tissue. Glycan analysis of primary human lymphatic endothelial cells (LEC) in their resting and activated states, in normal and tumour tissues and a comparison of the LEC glycan structures with those from blood vessel endothelial cells

2011-06-14 | E-GEOD-29933 | biostudies-arrayexpress

GATA2 knockout study to investigated the role of GATA2 in human hematopoiesis

Project description:We generated homozygous GATA2 knockout human embryonic stem cells (GATA2-/- hESCs) and analyzed their blood differentiation potential. Paritcularly at the hemogenic endothelium (HE) stage and hematopoietic progenitor cell (HPC) stage. Our result revealed that GATA2-/- hESCs displayed attenuated generation of CD34+CD43+ HPCs, due to the impairment of endothelial to hematopoietic transition (EHT). However, GATA2-/- hESCs retained the potential to generate erythroblasts, macrophages, but never granulocytes. Through RNA-Seq and further rescue experiment, we further identified that SPI1 was responsible for the defect of GATA2-/- hESCs in generation of CD34+CD43+ HPCs and granulocytes.

2017-02-09 | GSE69797 | GEO

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [ChIP-seq]

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [ChIP-seq]

| PRJNA532345 | ENA

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [RNA-seq]

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [RNA-seq]

| PRJNA532346 | ENA

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer (RNA-Seq)

Project description:Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer (RNA-Seq)

| PRJNA762903 | ENA