Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia; ARC Centre of Excellence in Plant Energy Biology, School of Molecular Sciences, The University of Western Australia, Perth, WA 6009, Australia.
Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Perth, WA 6009, Australia.
Cell. 2022 Nov 10;185(23):4428-4447.e28. doi: 10.1016/j.cell.2022.09.039. Epub 2022 Oct 31.
Human brain development is underpinned by cellular and molecular reconfigurations continuing into the third decade of life. To reveal cell dynamics orchestrating neural maturation, we profiled human prefrontal cortex gene expression and chromatin accessibility at single-cell resolution from gestation to adulthood. Integrative analyses define the dynamic trajectories of each cell type, revealing major gene expression reconfiguration at the prenatal-to-postnatal transition in all cell types followed by continuous reconfiguration into adulthood and identifying regulatory networks guiding cellular developmental programs, states, and functions. We uncover links between expression dynamics and developmental milestones, characterize the diverse timing of when cells acquire adult-like states, and identify molecular convergence from distinct developmental origins. We further reveal cellular dynamics and their regulators implicated in neurological disorders. Finally, using this reference, we benchmark cell identities and maturation states in organoid models. Together, this captures the dynamic regulatory landscape of human cortical development.
人类大脑的发育是由细胞和分子的重新配置所支撑的，这种重新配置一直持续到生命的第三个十年。为了揭示协调神经成熟的细胞动力学，我们以单细胞分辨率从妊娠到成年对人类前额叶皮层的基因表达和染色质可及性进行了分析。综合分析定义了每种细胞类型的动态轨迹，揭示了所有细胞类型在产前到产后过渡时的主要基因表达重新配置，然后持续重新配置到成年，并确定了指导细胞发育程序、状态和功能的调控网络。我们发现了表达动态与发育里程碑之间的联系，描述了细胞获得成人样状态的不同时间，并确定了来自不同发育起源的分子趋同。我们进一步揭示了与神经发育障碍相关的细胞动力学及其调控因子。最后，我们使用这个参考，对类器官模型中的细胞身份和成熟状态进行了基准测试。总之，这捕获了人类皮质发育的动态调控景观。
