干细胞模型揭示了产前人类脉络丛上皮亚型的顺序出现和收缩。
Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model.
发表日期:2024 Jun 17
作者:
Haley Masters, Shuxiong Wang, Christina Tu, Quy Nguyen, Yutong Sha, Matthew K Karikomi, Pamela Shi Ru Fung, Benjamin Tran, Cristina Martel, Nellie Kwang, Michael Neel, Olga G Jaime, Victoria Espericueta, Brett A Johnson, Kai Kessenbrock, Qing Nie, Edwin S Monuki
来源:
Brain Structure & Function
摘要:
尽管脉络丛上皮细胞(CPEC)在大脑稳态和修复中发挥着重要作用,但它们的发育谱系和多样性仍不清楚。在人类多能干细胞的简化分化中,衍生的 CPEC (dCPEC) 显示出典型的特性和与 Aβ 摄取相互作用的动态多纤毛表型。随着时间的推移,单个 dCPEC 转录组与人类类器官和胎儿 CPEC 密切相关,而伪颞叶和细胞周期分析则强调了 CPEC 直接起源于神经上皮细胞。此外,时间序列分析在早期时间点定义了代谢(1 型)和纤毛形成 dCPEC(2 型),随后随着 2 型细胞收缩,1 型多样化为合成代谢分泌型(1a 型)和分解代谢吸收亚型(1b 型) 。然后,这些时间模式在独立推导中得到确认,并使用人体组织映射到产前阶段。除了定义人类 CPEC 的产前谱系之外,这些发现还提出了 ChP 支持人类大脑发育的新动态模型。
Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with Aβ uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells. In addition, time series analyses defined metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contracted. These temporal patterns were then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest new dynamic models of ChP support for the developing human brain.