美国艾伦脑科学研究所曾红葵小组提出了小鼠视觉皮层发育中细胞类型的持续多样化。这一研究成果于2025年11月5日发表在国际顶尖学术期刊《自然》上。

在这里，研究小组提出了一个全面的和高分辨率的转录组和表观基因组细胞类型图谱的发展同主题视觉皮层。该图谱由568,654个高质量单细胞转录组的单细胞RNA测序数据集和200,061个高质量细胞核的单核多组数据集构建而成，这些数据集在胚胎和出生后发育阶段（从胚胎日11.5天到出生后56天）密集采样。该课题组人员通过计算重建了视觉皮层中所有兴奋性、抑制性和非神经元细胞类型的转录组发育轨迹图。分支点标志着新细胞类型在特定发育年龄的出现和细胞多样化的分子特征被确定。轨迹图显示，胚胎阶段的神经发生、胶质发生和早期有丝分裂后成熟以交错平行的方式产生了所有细胞类别和几乎所有亚类别。在整个出生后分化过程中出现了越来越精细的细胞类型，包括许多细胞类型在睁眼阶段和关键时期的出现，这表明在皮层发育的不同阶段存在持续的细胞类型多样化。在整个发育过程中，在特定细胞类型中存在着基因表达和染色质可及性的合作动态变化。研究组确定了细胞类型特异性和暂时解决的基因调控网络，通过可访问的染色质基序连接转录因子和下游靶基因。总的来说，他们的研究提供了与单个细胞类型和特定时间事件直接相关的详细动态分子图谱，可以揭示复杂和多方面皮层细胞类型和电路发育背后的分子逻辑。

据悉，哺乳动物皮层由高度多样化的细胞类型组成，并通过一系列暂时调节的事件进行发育。单细胞转录组学能够系统地研究皮层发育的整个时间轴上的细胞类型。

附：英文原文

Title: Continuous cell-type diversification in mouse visual cortex development

Author: Gao, Yuan, van Velthoven, Cindy T. J., Lee, Changkyu, Thomas, Emma D., Mathieu, Rmi, Ayala, Angela P., Barta, Stuard, Bertagnolli, Darren, Campos, Jazmin, Cardenas, Trangthanh, Carey, Daniel, Casper, Tamara, Chakka, Anish Bhaswanth, Chakrabarty, Rushil, Chiang, Megan, Ching, Lindsey, Clark, Michael, Desierto, Marie J., Ferrer, Rebecca, Gloe, Jessica, Goldy, Jeff, Guilford, Nathan, Guzman, Junitta, Halterman, Carliana R., Hastings, Samantha D., Hirschstein, Daniel, Ho, Windy, James, Katelyn, Juneau, Zoe, Martin, Naomi, McCue, Rachel, Meyerdierks, Emma, Mitchell, Amanda C., Nagra, Josh S., Nguy, Beagan, Nguyen, Thuc Nghi, Olsen, Paul, Oyama, Alana A., Pena, Nick, Quon, Jacob, Ren, Qingzhong, Ruiz, Augustin, Shapovalova, Nadiya V., Sulc, Josef, Torkelson, Amy, Tran, Alex, Tung, Herman, Valera Cuevas, Nasmil, Wang, Justin, Ariza, Jeanelle, McMillen, Delissa A. M., Waters, Jack, Kunst, Michael, Ronellenfitch, Kara, Levi, Boaz, Hawrylycz, Michael J., Pagan, Chelsea, Dee, Nick, Smith, Kimberly A., Tasic, Bosiljka, Yao, Zizhen, Zeng, Hongkui

Issue&Volume: 2025-11-05

Abstract: The mammalian cortex is composed of a highly diverse set of cell types and develops through a series of temporally regulated events1,2,3. Single-cell transcriptomics enables a systematic study of cell types across the entire timeline of cortical development. Here we present a comprehensive and high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex. The atlas is built from a single-cell RNA sequencing dataset of 568,654 high-quality single-cell transcriptomes and a single-nucleus Multiome dataset of 200,061 high-quality nuclei, which were densely sampled across the embryonic and postnatal developmental stages (from embryonic day11.5 to postnatal day56). We computationally reconstructed a transcriptomic developmental trajectory map of all excitatory, inhibitory and non-neuronal cell types in the visual cortex. Branching points that mark the emergence of new cell types at specific developmental ages and molecular signatures of cellular diversification are identified. The trajectory map shows that neurogenesis, gliogenesis and early postmitotic maturation in the embryonic stage give rise to all cell classes and nearly all subclasses in a staggered parallel manner. Increasingly refined cell types emerge throughout the postnatal differentiation process, including the late emergence of many cell types during the eye-opening stage and the onset of critical period, suggesting that there is continuous cell-type diversification at different stages of cortical development. Throughout development, there are cooperative dynamic changes in gene expression and chromatin accessibility in specific cell types. We identify cell-type-specific and temporally resolved gene regulatory networks that link transcription factors and downstream target genes through accessible chromatin motifs. Collectively, our study provides a detailed dynamic molecular map directly associated with individual cell types and specific temporal events that can reveal the molecular logic underlying the complex and multifaceted cortical cell type and circuit development.

DOI: 10.1038/s41586-025-09644-1

Source: https://www.nature.com/articles/s41586-025-09644-1