人类胎儿大脑自组织成长期扩张的器官
Delilah Hendriks1, Anna Pagliaro2, Francesco Andreatta2
1Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.
Cell
|January 9, 2024
概括
健康的人类胎儿大脑组织自组织成可扩展的器官 (FeBOs),模仿体内发育. 这种新平台可以长期研究大脑发育以及包括脑癌在内的疾病.
科学领域:
- 神经科学
- 发育生物学
- 干细胞生物学
背景情况:
- 人类大脑的发育涉及复杂的神经元扩张和组织架构的建立.
- 目前的大脑器官完全来自多能干细胞.
- 需要替代器官模型来更好地回顾体内发育.
研究的目的:
- 研究健康的人类胎儿大脑组织的自我组织到可扩展的有机体 (FeBOs).
- 描述FeBOs的细胞异质性和组织.
- 建立FeBOs作为研究中枢神经系统 (CNS) 发展和疾病的补充平台.
主要方法:
- 在体外培养健康的人类胎儿大脑组织以促进自我组织成有机体 (FeBOs).
- 评估FeBO扩张,组织完整性和细胞外矩阵 (ECM) 利基维护.
- 来自不同中枢神经系统区域的FeBO线来评估区域身份的保存.
- 使用CRISPR-Cas9基因编辑生成突变的FeBO线路用于疾病建模.
主要成果:
- 健康的人类胎儿大脑组织自发地形成有机体 (FeBOs).
- 在体内细胞异质性和复杂组织中FeBO的表,并且可以长期扩展.
- FeBO的生长取决于组织完整性和ECM位,使其能够持续扩张.
- 来自不同中枢神经系统区域的FeBO保持了区域性特征.
- 为大脑癌症研究生成了同基因突变FeBO线.
结论:
- FeBOs代表了直接从胎儿大脑组织中获得的新型和可扩展的器官模型.
- 这个平台总结了人类大脑发育和组织的关键方面.
- 对于研究中枢神经系统发育,位置认同和脑癌的现有有机体模型,FeBO提供了一种补充方法.
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