Laboratory of Stem Cell and Neuro-Vascular Biology, Cell and Development Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.
Biol Open. 2022 Sep 15;11(9). doi: 10.1242/bio.059510.
Recent genetic lineage tracing studies reveal heterogeneous origins of vascular endothelial cells and pericytes in the developing brain vasculature, despite classical experimental evidence for a mesodermal origin. Here we provide evidence through a genetic lineage tracing experiment that cephalic paraxial mesodermal cells give rise to endothelial cells and pericytes in the developing mouse brain. We show that Hepatic leukemia factor (Hlf) is transiently expressed by cephalic paraxial mesenchyme at embryonic day (E) 8.0-9.0 and the genetically marked E8.0 Hlf-expressing cells mainly contribute to the developing brain vasculature. Interestingly, the genetically marked E10.5 Hlf-expressing cells, which have been previously reported to contain embryonic hematopoietic stem cells, fail to contribute to the vascular cells. Combined, our genetic lineage tracing data demonstrate that a transient expression of Hlf marks a cephalic paraxial mesenchyme contributing to the developing brain vasculature. This article has an associated First Person interview with the first author of the paper.
最近的遗传谱系追踪研究揭示了发育中脑脉管系统内皮细胞和周细胞的异质性起源，尽管有经典的实验证据表明其来源于中胚层。在这里，我们通过遗传谱系追踪实验提供了证据，表明头侧轴旁中胚层细胞在发育中的小鼠脑中产生内皮细胞和周细胞。我们表明，肝母细胞瘤因子 (Hlf) 在胚胎期 (E) 8.0-9.0 时由头侧轴旁间充质短暂表达，并且遗传标记的 E8.0 Hlf 表达细胞主要有助于脑脉管系统的发育。有趣的是，先前报道含有胚胎造血干细胞的遗传标记的 E10.5 Hlf 表达细胞未能有助于血管细胞的形成。综合来看，我们的遗传谱系追踪数据表明，Hlf 的短暂表达标志着有助于脑脉管系统发育的头侧轴旁间充质。本文附有该论文第一作者的第一人称采访。
