人类皮层类器官重现婴儿脑生长轨迹的个体间差异，这一成果由北卡罗来纳大学Jason L. Stein团队经过不懈努力而取得。2025年12月22日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

该研究团队从婴儿脑成像研究的18名参与者中每个人产生了多达3个iPSC克隆，他们在婴儿期接受了纵向脑成像。该课题组人员在同一参与者的克隆中发现了一致的hCO形态和皮质细胞类型。hCO横截面积和褶襞/脉络膜丛的产生与体内皮质生长速率有关。在命运决定轨迹的关键位置，细胞周期相关基因在早期祖细胞中的表达与6至12个月大的皮质生长速率相关，并且富集了小头畸形和神经发育障碍基因。他们的数据表明，hCOs捕获了影响婴儿皮层表面积扩张的皮质细胞类型的个体间差异。

研究人员表示，诱导多能干细胞（iPSC）衍生的人类皮质类器官（hCOs）在个体遗传背景下模拟神经发生。hCO表型在多大程度上概括了参与者的大脑生长，而这些参与者的大脑生长来源于hCO表型，目前还没有得到很好的证实。

附：英文原文

Title: Human cortical organoids recapitulate inter-individual variability in infant brain-growth trajectories

Author: Madison R. Glass, Nana Matoba, Alvaro A. Beltran, Niyanta K. Patel, Tala M. Farah, Karthik Eswar, Shivam Bhargava, Karen Huang, Ian Curtin, Sara Ahmed, Mary Srivastava, Emma Drake, Liam T. Davis, Meghana Yeturi, Kexin Sun, Michael I. Love, Jeremy M. Simon, Tanya St. John, Natasha Marrus, Juhi Pandey, Annette Estes, Stephen Dager, Robert T. Schultz, Kelly Botteron, Alan Evans, Sun Hyung Kim, Martin Styner, Robert C. McKinstry, D. Louis Collins, Heather Volk, Kelly Benke, Lonnie Zwaigenbaum, Heather Hazlett, Adriana S. Beltran, Jessica B. Girault, Mark D. Shen, Joseph Piven, Jason L. Stein

Issue&Volume: 2025-12-22

Abstract: Induced pluripotent stem cell (iPSC)-derived human cortical organoids (hCOs) model neurogenesis on an individual’s genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from whom they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who underwent longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of hem/choroid plexus were associated with in vivo cortical growth rates. Cell-cycle-associated gene expression in early progenitors at the crux of fate-decision trajectories was correlated with cortical growth rates from 6 to 12 months of age and was enriched for microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types that influences infant cortical surface area expansion.

DOI: 10.1016/j.stem.2025.12.001

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00435-7