奥地利科学院分子生物技术研究所Jürgen A. Knoblich、Christopher Esk团队的研究显示，脑类器官具有动态克隆生长和可调的组织补充能力。2024年5月7日，国际学术期刊《自然-细胞生物学》发表了这一成果。

研究人员在三维人脑类器官组织中通过基因组DNA条形码实现了全组织系谱追踪，并发现由单个干细胞克隆产生的后代变化很大。通过随机建模，研究发现不同谱系的大小是由于谱系亚群保留了对称分裂的细胞。研究人员通过化学消除或基因限制嵌合有机体中的一个细胞亚群发现在生长受到干扰后，细胞系的大小可以根据组织需求进行调整。该研究数据表明，干细胞群的适应可塑性确保了人脑器官组织发育的稳定性。

据了解，在大脑发育过程中，神经祖细胞通过对称分裂扩增，通过不对称分裂产生分化的细胞类型。不同神经干细胞在这些模式之间的转换各不相同，从而形成不同大小的克隆。基于成像的系谱示踪可进行高细胞分辨率的系谱分析，但目前还缺乏分析整个组织克隆行为的方法。

附：英文原文

Title: Cerebral organoids display dynamic clonal growth and tunable tissue replenishment

Author: Lindenhofer, Dominik, Haendeler, Simon, Esk, Christopher, Littleboy, Jamie B., Brunet Avalos, Clarisse, Naas, Julia, Pflug, Florian G., van de Ven, Eline G. P., Reumann, Daniel, Baffet, Alexandre D., von Haeseler, Arndt, Knoblich, Jrgen A.

Issue&Volume: 2024-05-07

Abstract: During brain development, neural progenitors expand through symmetric divisions before giving rise to differentiating cell types via asymmetric divisions. Transition between those modes varies among individual neural stem cells, resulting in clones of different sizes. Imaging-based lineage tracing allows for lineage analysis at high cellular resolution but systematic approaches to analyse clonal behaviour of entire tissues are currently lacking. Here we implement whole-tissue lineage tracing by genomic DNA barcoding in 3D human cerebral organoids, to show that individual stem cell clones produce progeny on a vastly variable scale. By using stochastic modelling we find that variable lineage sizes arise because a subpopulation of lineages retains symmetrically dividing cells. We show that lineage sizes can adjust to tissue demands after growth perturbation via chemical ablation or genetic restriction of a subset of cells in chimeric organoids. Our data suggest that adaptive plasticity of stem cell populations ensures robustness of development in human brain organoids.

DOI: 10.1038/s41556-024-01412-z

Source: https://www.nature.com/articles/s41556-024-01412-z