Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
Sci Rep. 2020 Nov 23;10(1):20393. doi: 10.1038/s41598-020-77297-3.
Brain embryonic periventricular endothelial cells (PVEC) crosstalk with neural progenitor cells (NPC) promoting mutual proliferation, formation of tubular-like structures in the former and maintenance of stemness in the latter. To better characterize this interaction, we conducted a comparative transcriptome analysis of mouse PVEC vs. adult brain endothelial cells (ABEC) in mono-culture or NPC co-culture. We identified > 6000 differentially expressed genes (DEG), regardless of culture condition. PVEC exhibited a 30-fold greater response to NPC than ABEC (411 vs. 13 DEG). Gene Ontology (GO) analysis of DEG that were higher or lower in PVEC vs. ABEC identified "Nervous system development" and "Response to Stress" as the top significantly different biological process, respectively. Enrichment in canonical pathways included HIF1A, FGF/stemness, WNT signaling, interferon signaling and complement. Solute carriers (SLC) and ABC transporters represented an important subset of DEG, underscoring PVEC's implication in blood-brain barrier formation and maintenance of nutrient-rich/non-toxic environment. Our work characterizes the gene signature of PVEC and their important partnership with NPC, underpinning their unique role in maintaining a healthy neurovascular niche, and in supporting brain development. This information may pave the way for additional studies to explore their therapeutic potential in neuro-degenerative diseases, such as Alzheimer's and Parkinson's disease.
脑胚胎室管膜内皮细胞 (PVEC) 与神经祖细胞 (NPC) 相互交流，促进彼此的增殖，前者形成管状结构，后者维持干细胞状态。为了更好地描述这种相互作用，我们对小鼠 PVEC 与成年脑内皮细胞 (ABEC) 在单独培养或 NPC 共培养中的转录组进行了比较分析。无论培养条件如何，我们都鉴定出了超过 6000 个差异表达基因 (DEG)。与 ABEC 相比，PVEC 对 NPC 的反应要强 30 倍 (411 个 vs. 13 个 DEG)。对 PVEC 中高于或低于 ABEC 的 DEG 的基因本体论 (GO) 分析分别确定了“神经系统发育”和“应激反应”为差异最大的生物学过程。包含 HIF1A、FGF/干细胞、WNT 信号、干扰素信号和补体的经典途径也得到了富集。溶质载体 (SLC) 和 ABC 转运蛋白是 DEG 的一个重要子集，这突出了 PVEC 对血脑屏障形成和维持富含营养/无毒环境的重要性。我们的工作描述了 PVEC 的基因特征及其与 NPC 的重要伙伴关系，这为它们在维持健康的神经血管生态位和支持大脑发育方面的独特作用提供了依据。这些信息可能为进一步研究探索它们在神经退行性疾病（如阿尔茨海默病和帕金森病）中的治疗潜力铺平道路。
