美国加州大学旧金山分校Eric J. Huang、Elizabeth E. Crouch等研究人员合作发现，内皮细胞和壁细胞的促进产前人脑的血管生成。相关论文于2022年9月29日发表在《细胞》杂志上。
利用荧光激活细胞分选、单细胞转录组学以及组织学和超微结构分析，研究人员表明，在第二妊娠期期间，内皮细胞和壁细胞亚型的集合体在大脑血管中形成。这些血管细胞遵循不同的发育轨迹，利用不同的信号机制，包括胶原蛋白、层粘连蛋白和中期因子，以促进细胞间的交流和成熟。有趣的是，研究结果显示，顶端细胞（内皮细胞的一个亚型）在脑室区附近高度富集，而脑室区是神经发生活跃的地方。与这些观察一致，移植到皮层器官中的产前血管细胞表现出限制性的谱系潜力，有利于顶端细胞，促进神经发生，并减少细胞压力。总之，这些研究结果揭示了在人类大脑发育的这个关键时期血管成熟的重要机制。
据介绍，血管生成和神经生成之间的相互作用调节着胚胎期的大脑发育。然而，对血管细胞成熟的阶段缺乏全面的了解，特别是在产前的人类大脑中。
附：英文原文
Title: Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain
Author: Elizabeth E. Crouch, Aparna Bhaduri, Madeline G. Andrews, Arantxa Cebrian-Silla, Loukas N. Diafos, Janeth Ochoa Birrueta, Kaylee Wedderburn-Pugh, Edward J. Valenzuela, Neal K. Bennett, Ugomma C. Eze, Carmen Sandoval-Espinosa, Jiapei Chen, Cristina Mora, Jayden M. Ross, Clare E. Howard, Susana Gonzalez-Granero, Jaime Ferrer Lozano, Maximo Vento, Maximilian Haeussler, Mercedes F. Paredes, Ken Nakamura, Jose Manuel Garcia-Verdugo, Arturo Alvarez-Buylla, Arnold R. Kriegstein, Eric J. Huang
Issue&Volume: 2022/09/29
Abstract: Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and histological and ultrastructural analyses, we show that an ensemble of endothelial and mural cell subtypes tile the brain vasculature during the second trimester. These vascular cells follow distinct developmental trajectories and utilize diverse signaling mechanisms, including collagen, laminin, and midkine, to facilitate cell-cell communication and maturation. Interestingly, our results reveal that tip cells, a subtype of endothelial cells, are highly enriched near the ventricular zone, the site of active neurogenesis. Consistent with these observations, prenatal vascular cells transplanted into cortical organoids exhibit restricted lineage potential that favors tip cells, promotes neurogenesis, and reduces cellular stress. Together, our results uncover important mechanisms into vascular maturation during this critical period of human brain development.
DOI: 10.1016/j.cell.2022.09.004
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01126-6