Cerebral organoids offer an opportunity to bioengineer experimental avatars of the developing human brain and have already begun garnering relevant insights into complex neurobiological processes and disease. Thus far, investigations into their heterogeneous cellular composition and developmental trajectories have been largely limited to transcriptional readouts. Recent advances in global proteomic technologies have enabled a new range of techniques to explore dynamic and non-overlapping spatiotemporal protein-level programs operational in these humanoid neural structures. Here we discuss these early protein-based studies and their potentially essential role for unraveling critical secreted paracrine signals, processes with poor proteogenomic correlations, or neurodevelopmental proteins requiring post-translational modification for biological activity. Integrating emerging proteomic tools with these faithful human-derived neurodevelopmental models could transform our understanding of complex neural cell phenotypes and neurobiological processes, not exclusively driven by transcriptional regulation. These insights, less accessible by exclusive RNA-based approaches, could reveal new knowledge into human brain development and guide improvements in neural regenerative medicine efforts.

大脑类器官为开发人类大脑的生物工程实验化身提供了机会，并且已经开始获得对复杂神经生物学过程和疾病的相关见解。迄今为止，对其异质性细胞组成和发育轨迹的研究主要限于转录读数。全球蛋白质组学技术的最新进展使一系列新的技术能够探索在这些类人神经结构中运行的动态和非重叠时空蛋白质水平程序。在这里，我们讨论了这些基于蛋白质的早期研究及其在揭示关键的分泌性旁分泌信号、蛋白质组学相关性差的过程中的潜在重要作用，或需要对生物活性进行翻译后修饰的神经发育蛋白。将新兴的蛋白质组学工具与这些忠实的人类衍生神经发育模型相结合，可以改变我们对复杂神经细胞表型和神经生物学过程的理解，而不仅仅是由转录调控驱动。这些见解不太可能通过基于 RNA 的独家方法获得，但可以揭示人类大脑发育的新知识，并指导神经再生医学工作的改进。