SNIC SUPR
fishlymphatics
Dnr:

SNIC 2019/8-209

Type:

SNIC Small Compute

Principal Investigator:

Kaska Koltowska

Affiliation:

Uppsala universitet

Start Date:

2019-06-05

End Date:

2021-07-01

Primary Classification:

10614: Developmental Biology

Webpage:

Allocation

Abstract

The lymphatic system is important for fluid homeostasis, immune function, fat absorption and waste removal. The lymphatic endothelial cell progenitors (LEC) sprout from the posterior cardinal vein (PCV) and migrate to form distinct vascular network. It is well established that the expression of Prox1, a transcription factor, chiefly marks specified LECs. Prox1-positive LEC precursors are biopotential and upon cell division one daughter cell upregulates Prox1 expression and becomes a LEC, while the other daughter cell downregulates Prox1 and remains in the venous endothelial cell (VEC). This suggests a high degree of plasticity within the venous endothelium and possible cellular heterogeneity within the PCV. In order to understand how this the cellular and molecular variation is achieved and how LEC identity is refined during development we are using whole-genome approaches in combination with live imaging in the zebrafish embryo. During development, dynamic chromatin changes ensure the robustness of cell specification and we aim to define the specific epigenetic state that is required for a cell to become a LEC by using ATAC-sequencing. In addition, we are using single cell RNA-sequencing to identify genes that mark LEC fate and identify differences between LEC progenitors. Using bioinformatic analysis we will combine the two data set to uncover chromatin landscapes in relation to LEC specific gene expression. We hope that this may shed light on how LEC fate is regulated and how this lineage becomes restricted during development.