Chen Jiapei, Choi Jennifer Ja-Yoon, Lin Pin-Yeh, Huang Eric J
Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Department of Pathology, University of California, San Francisco, California, USA.
Annu Rev Pathol. 2025 Jan;20(1):221-243. doi: 10.1146/annurev-pathmechdis-111523-023446. Epub 2025 Jan 2.
The germinal matrix harbors neurogenic niches in the subpallium of the prenatal human brain that produce abundant GABAergic neurons. In preterm infants, the germinal matrix is particularly vulnerable to developing hemorrhage, which disrupts neurogenesis and causes severe neurodevelopmental sequelae. However, the disease mechanisms that promote germinal matrix hemorrhage remain unclear. Here, we review recent advances using single-cell transcriptomics to uncover novel mechanisms that govern neurogenesis and angiogenesis in the germinal matrix of the prenatal human brain. These approaches also reveal the critical role of immune-vascular interaction that promotes vascular morphogenesis in the germinal matrix and how proinflammatory factors from activated neutrophils and monocytes can disrupt this process, leading to hemorrhage. Collectively, these results reveal fundamental disease mechanisms and therapeutic interventions for germinal matrix hemorrhage.
生发基质在产前人类大脑的皮质下包含神经源性微环境，可产生大量的γ-氨基丁酸能神经元。在早产儿中，生发基质特别容易发生出血，这会破坏神经发生并导致严重的神经发育后遗症。然而，促进生发基质出血的疾病机制仍不清楚。在此，我们综述了利用单细胞转录组学揭示产前人类大脑生发基质中神经发生和血管生成调控新机制的最新进展。这些方法还揭示了免疫-血管相互作用在促进生发基质血管形态发生中的关键作用，以及活化的中性粒细胞和单核细胞产生的促炎因子如何破坏这一过程，导致出血。总的来说，这些结果揭示了生发基质出血的基本疾病机制和治疗干预措施。
