Guo Xueyu, Lee Trevor, Sun Jason, Sun Julianne, Cai Wenjie, Yang Qingwei, Sun Tao
Center for Precision Medicine, Huaqiao University, Xiamen, Fujian, 361021, China.
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY, 10065, USA.
Adv Sci (Weinh). 2024 Dec;11(47):e2407137. doi: 10.1002/advs.202407137. Epub 2024 Nov 4.
The expansion of neural progenitors and production of distinct neurons are crucial for architectural assembly and formation of connectivity in human brains. Subplate neurons (SPNs) are among the firstborn neurons in the human fetal cerebral cortex, and play a critical role in establishing intra- and extracortical connections. However, little is known about SPN origin and developmental lineages. In this study, spatial landscapes and molecular trajectories of SPNs in the human fetal cortices from gestational weeks (GW) 10 to 25 are created by performing spatial transcriptomics and single-cell RNA sequencing. Genes known to be evolutionarily human-specific and genes associated with extracellular matrices (ECMs) are found to maintain stable proportions of subplate neurons among other neuronal types. Enriched ECM gene expression in SPNs varies in distinct cortical regions, with the highest level in the frontal lobe of human fetal brains. This study reveals molecular origin and lineage specification of subplate neurons in the human fetal cerebral cortices, and highlights underpinnings of SPNs to cortical neurogenesis and early structural folding.
神经祖细胞的扩增和不同神经元的产生对于人类大脑的结构组装和连接形成至关重要。板下神经元（SPNs）是人类胎儿大脑皮层中最早产生的神经元之一，在建立皮质内和皮质外连接中起关键作用。然而，关于SPN的起源和发育谱系知之甚少。在本研究中，通过进行空间转录组学和单细胞RNA测序，创建了妊娠周数（GW）10至25的人类胎儿皮质中SPN的空间图谱和分子轨迹。发现已知在进化上具有人类特异性的基因以及与细胞外基质（ECM）相关的基因在其他神经元类型中维持板下神经元的稳定比例。SPN中富集的ECM基因表达在不同的皮质区域有所不同，在人类胎儿大脑额叶中水平最高。本研究揭示了人类胎儿大脑皮层中板下神经元的分子起源和谱系特化，并强调了SPN对皮质神经发生和早期结构折叠的支撑作用。
