Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
ECCPS Bioinformatics and Deep Sequencing Platform, Max Planck Institute for Heart and Lung Research, Bad Nauheim 61231, Germany.
Development. 2019 Jun 3;146(11):dev173427. doi: 10.1242/dev.173427.
The development of a vascular network is essential to nourish tissues and sustain organ function throughout life. Endothelial cells (ECs) are the building blocks of blood vessels, yet our understanding of EC specification remains incomplete. Zebrafish mutants have been used broadly as an avascular model, but little is known about the molecular mechanisms of action of the Npas4l transcription factor. Here, to identify its direct and indirect target genes, we have combined complementary genome-wide approaches, including transcriptome analyses and chromatin immunoprecipitation. The cross-analysis of these datasets indicates that Npas4l functions as a master regulator by directly inducing a group of transcription factor genes that are crucial for hematoendothelial specification, such as , and We also identified new targets of Npas4l and investigated the function of a subset of them using the CRISPR/Cas9 technology. Phenotypic characterization of mutants reveals a novel player in developmental angiogenesis, confirming the reliability of the datasets generated. Collectively, these data represent a useful resource for future studies aimed to better understand EC fate determination and vascular development.
血管网络的发展对于滋养组织和维持器官功能至关重要。内皮细胞（ECs）是血管的组成部分，但我们对 EC 特化的理解仍不完整。斑马鱼突变体已被广泛用作无血管模型，但关于 Npas4l 转录因子的作用机制知之甚少。在这里，为了鉴定其直接和间接靶基因，我们结合了互补的全基因组方法，包括转录组分析和染色质免疫沉淀。这些数据集的交叉分析表明，Npas4l 通过直接诱导一组对于造血内皮特化至关重要的转录因子基因，充当主调控因子，如 、 和 。我们还鉴定了 Npas4l 的新靶基因，并使用 CRISPR/Cas9 技术研究了其中一部分靶基因的功能。 突变体的表型特征揭示了发育血管生成中的一个新参与者，证实了生成数据集的可靠性。总的来说，这些数据为未来旨在更好地理解 EC 命运决定和血管发育的研究提供了有用的资源。
