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中皮和内皮的共同发育使肺部和肠道器官的器官类型血管化成为可能

Yifei Miao¹, Nicole M Pek¹, Cheng Tan¹

¹Division of Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center (CCHMC), Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Center for Stem Cell and Organoid Medicine (CuSTOM), CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Division of Developmental Biology, CCHMC, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.

|July 1, 2025

概括

这项研究从诱导多能干细胞 (iPSC) 开发了血管化器官,以模拟人体器官发育和疾病. 这些器官模仿器官特异性血管,有助于理解内皮细胞相互作用.

科学领域:

发育生物学
干细胞生物学
机器人技术

背景情况:

器官的发育依赖于复杂的微环境和细胞之间的相互作用.
血管和介质细胞的器官特征对生理功能至关重要.

研究的目的:

从IPSC中共同区分中皮和内皮,以产生血管化的肺和肠道器官.
研究骨形态蛋白 (BMP) 信号在调节原生细胞比例中的作用.
分析特定器官的基因特征和内皮特征.

主要方法:

诱导多能干细胞 (iPSC) 共同分化为中皮和内皮.
用于基因表达分析的单细胞RNA测序 (scRNA-seq).
对小鼠进行器官移植以评估血管整合和成熟.

主要成果:

对特定组织的原始体进行精确控制的内皮与中皮比率.
通过sc-RNA测序确定了器官特异性的内皮和介质细胞特征.
血管化器官表现出组织特异性屏障功能和增强的成熟,包括气泡形成.
移植的器官与宿主循环结合,保持器官特异性并促进成熟.
在患有分叉盒F1 (FOXF1) 突变的患者中发现了异常的内皮-上皮交叉声.

结论:

多系器官为研究人类器官生成和疾病提供了强大的平台.
这种模型有助于研究细胞间的发育和病理.
这项研究揭示了FOXF1相关疾病中的内皮-上皮交叉声.

关键词:

其他类型协同区分皮肤内皮在肠道一个肺介质细胞中皮层特定器官内皮有机物血管化

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