New reporter zebrafish line unveils heterogeneity among lymphatic endothelial cells during development

다국어 초록 (Multilingual Abstract)

In zebrafish, lymphatic endothelial cells (LECs) originate from multiple/several distinct progenitor populations and generate organ‐specific lymphatic vasculatures. Cell fate and tissue specificities were determined using a combination of genetically engineered transgenic lines in which the promoter of a LEC‐specific gene drives expression of a fluorescent reporter protein.
We established a novel zebrafish transgenic line expressing eGFP under the control of part of the zebrafish batf3 promoter (Basic Leucine Zipper ATF‐Like Transcription Factor 3). Spatiotemporal examination of Tg(batf3MIN:eGFP) transgenic fish revealed a typical lymphatic expression pattern, which does not perfectly recapitulate the expression pattern of existing LEC transgenic lines. eGFP+ cells constitute a heterogeneous endothelial cell population, which expressed LEC and/or blood endothelial cells (BEC) markers in different tissues. In addition, we characterize the renal eGFP+ cell as a population of interest to study kidney diseases and regeneration.
Our Tg(batf3MIN:eGFP) reporter zebrafish line provides a useful system to study LEC populations, of which heterogeneity depends on origin of progenitors, tissue environment and physiological conditions. We further developed a novel fish‐adapted tissue clearing method, which allows deep imaging and 3D‐visualization of vascular and lymphatic networks in the whole organism.

Tg(batf3MIN:eGFP) is a novel zebrafish transgenic line useful to study vascular and lymphatic networks.
Tg(batf3MIN:eGFP) fish phenotyping reveals the heterogeneity of lymphatic endothelial cells (LEC) in different tissue environments.
Tg(batf3MIN:eGFP) fish pattern does not perfectly overlap the expression of the canonical lymphatic molecular marker lyve1 suggesting the existence of distinct LEC subpopulations.
By its expression in interstitial cells of the kidney, Tg(batf3MIN:eGFP) constitutes a novel tool to study human renal diseases and conduct in vivo drug screening.