加州大学Joseph G. Gleeson小组宣布他们研发了神经发育障碍的表型脑类器官图谱和生物库。2025年11月3日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

为了填补这些空白，研究组提出了一个由加州再生医学研究所（CIRM）发起的NDD生物库，其中包含352个公开可用的遗传多样性患者来源的诱导多能干细胞（iPSCs），以及临床细节、脑成像和基因组数据，代表了它们的主要疾病类别：小头畸形（MIC）、多小回症（PMG）、癫痫（EPI）和智力残疾（ID）。从35名代表性患者中，该团队研究了6000多个脑类器官的组织学和单细胞转录组学。与来自10个典型神经系统的类器官文库相比，患者表现出与潜在临床疾病类别相关的明显细胞缺陷。MIC表现为细胞存活缺陷，TTR+细胞过多，PMG表现为中间祖细胞连接缺陷，EPI表现为星形胶质细胞过多，ID表现为TTR+细胞过量生成。他们的类器官图谱显示了保守的和不同的NDD类别特异性表型，桥接基因型和表型。这个NDD iPSC生物库可以支持未来的疾病建模和治疗方法。

据了解，基因的缺失与神经发育障碍（NDDs）有关，但机制和靶向治疗仍不清楚。

附：英文原文

Title: A phenotypic brain organoid atlas and biobank for neurodevelopmental disorders

Author: Lu Wang, Yuji Nakamura, Junhao Li, David Sievert, Yang Liu, Toan Nguyen, Prudhvi Sai Jetti, Ethan Thai, Rachel Yibei Zhou, Jiaming Weng, Naomi Meave, Manya Yadavilli, Robyn Howarth, Kevin Camey, Niyati Banka, Charlotte Owusu-Hammond, Chelsea Barrows, Stephen F. Kingsmore, Maha S. Zaki, Eran Mukamel, Joseph G. Gleeson

Issue&Volume: 2025-11-03

Abstract: Thousands of genes are associated with neurodevelopmental disorders (NDDs), yet mechanisms and targeted treatments remain elusive. To fill these gaps, we present a California Institute of Regenerative Medicine (CIRM)-initiated NDD biobank of 352 publicly available genetically diverse patient-derived induced pluripotent stem cells (iPSCs), along with clinical details, brain imaging, and genomic data, representing four major categories of disease: microcephaly (MIC), polymicrogyria (PMG), epilepsy (EPI), and intellectual disability (ID). From 35 representative patients, we studied over 6,000 brain organoids for histology and single-cell transcriptomics. Compared with an organoid library from ten neurotypicals, patients showed distinct cellular defects linked to underlying clinical disease categories. MIC showed defects in cell survival and excessive TTR+ cells, PMG showed intermediate progenitor cell junction defects, EPI showed excessive astrogliosis, and ID showed excessive generation of TTR+ cells. Our organoid atlas demonstrates both conserved and divergent NDD category-specific phenotypes, bridging genotype and phenotype. This NDD iPSC biobank can support future disease modeling and therapeutic approaches.

DOI: 10.1016/j.stem.2025.10.006

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00374-1