Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA,
Quantitative Life Sciences, McGill University, Montreal, Québec, Canada.
Dev Neurosci. 2021;43(6):321-334. doi: 10.1159/000518351. Epub 2021 Jul 15.
Angiopoietin1 (Angpt1) is a secreted protein that activates the endothelial Tie2 receptor. Angpt1 plays a critical role in cardiac development and vascular remodeling in response to disease or injury and shows cell type-restricted expression in the lung, eye, and hematopoietic system. However, the expression of Angpt1 in the developing and adult brain is not known. Here, we employ Angpt1-GFP knock-in reporter mice and a systematic analysis of multiple single-cell RNA sequencing datasets to map the expression of Angpt1 during brain development and adulthood. In the developing brain, Angpt1 displays specific spatiotemporal patterns, with strong expression in cerebellar GABA interneuron progenitors and, to a lower level, in glial progenitor and astrocyte lineages. In the adult brain, on the other hand, we show that neurons are the main source of Angpt1 in the cerebrum, while in the cerebellum, expression is mostly restricted to astrocytes. Together, our data provide clarity on the cell types that express Angpt1 in the developing and adult brain and can be utilized to guide future studies, examining Angpt1 function in brain development, homeostasis, and pathological conditions.
血管生成素 1(Angpt1)是一种分泌蛋白,可激活内皮 Tie2 受体。Angpt1 在心脏发育和血管重塑中起着关键作用,可响应疾病或损伤,并且在肺、眼和造血系统中表现出细胞类型特异性表达。然而,在发育中的和成年的大脑中 Angpt1 的表达尚不清楚。在这里,我们使用 Angpt1-GFP 敲入报告小鼠和对多个单细胞 RNA 测序数据集的系统分析,来描绘 Angpt1 在大脑发育和成年期的表达模式。在发育中的大脑中,Angpt1 显示出特定的时空表达模式,在小脑 GABA 中间神经元祖细胞中表达强烈,而在神经胶质祖细胞和星形胶质细胞谱系中的表达水平较低。另一方面,在成年大脑中,我们表明神经元是大脑中 Angpt1 的主要来源,而在小脑,表达主要局限于星形胶质细胞。总之,我们的数据为发育中和成年大脑中表达 Angpt1 的细胞类型提供了明确的信息,并可用于指导未来的研究,研究 Angpt1 在大脑发育、稳态和病理条件下的功能。