科学家使用单细胞组学技术揭示了指导前额叶皮层发育和成熟的关键基因调控网络

中文摘要

人类大脑发育的基础是从出生持续到生命第三个十年的细胞和分子重构。为了揭示协调神经发育成熟的细胞动力学规律，研究人员分析了人类前额叶皮层基因表达和染色质在妊娠期至成年期单细胞分辨率下的可及性。他们的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从产前到产后转变的主要基因表达重组成分，且这种基因表达重组一直持续到成年，他们还鉴定了引导细胞发育、活动状态和功能的调控网络。他们揭示了表达动力学和发育里程碑之间的联系，界定了细胞获得成人样状态的不同时间，并从不同的发育起源中鉴定了分子趋同。此外，他们还进一步揭示了与神经系统疾病有关的细胞动力学及其调节因子。最后，利用这一参考，他们对类器官模型中的细胞身份和成熟状态进行了鉴定。总之，他们的研究捕捉到了人类皮层发育的动态调控图谱。

英文摘要

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 perse 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.