人类血管类器官发育过程中的命运和状态转变，这一成果由瑞士苏黎世联邦理工学院Barbara Treutlein研究组经过不懈努力而取得。2025年4月17日出版的《细胞》杂志发表了这一最新研究成果。

课题组研究人员将单细胞多组学与遗传和信号通路扰动结合起来重建hBVO的发育。中胚层祖细胞在体外分化为内皮细胞和壁祖细胞，异种移植的BVOs获得明确的动静脉内皮细胞特征。该研究团队推断基因调控网络和主题单细胞遗传扰动，以确定参与细胞命运规范的转录因子（TFs）和受体，包括MECOM在内皮和壁规范中的作用。课题组评估了BVOs产生器官型状态的潜力，确定了hBVOs中缺乏表达的TF，并发现诱导的LEF1过表达增加了脑血管特异性。最后，小组将血管疾病相关基因映射到hBVO细胞状态，并分析了糖尿病的hBVO模型。总之，该课题组提供了hBVO发育的全面细胞状态图谱，并阐明了hBVO在转化研究中的作用和局限性。

据了解，人类血管类器官（hBVOs）已成为模拟人类血管发育和疾病的系统。

附：英文原文

Title: Fate and state transitions during human blood vessel organoid development

Author: Marina T. Nikolova, Zhisong He, Makiko Seimiya, Gustav Jonsson, Wuji Cao, Ryo Okuda, Reiner A. Wimmer, Ryoko Okamoto, Josef M. Penninger, J. Gray Camp, Barbara Treutlein

Issue&Volume: 2025-04-17

Abstract: Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use single-cell multi-omics together with genetic and signaling pathway perturbations to reconstruct hBVO development. Mesodermal progenitors bifurcate into endothelial and mural fates in vitro, and xenografted BVOs acquire definitive arteriovenous endothelial cell specification. We infer a gene regulatory network and use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, identify TFs lacking expression in hBVOs, and find that induced LEF1 overexpression increases brain vasculature specificity. Finally, we map vascular disease-associated genes to hBVO cell states and analyze an hBVO model of diabetes. Altogether, we provide a comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research.

DOI: 10.1016/j.cell.2025.03.037

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00387-3