Decoding the spatiotemporal development of human meninges

Yanxin Li; Zhongqiu Li; Yong She; Ziqing He; Changliang Wang; Yuehong Zhang; Rong Li; Lei Jin; Fen Ji; Peng Du; Ji Dong; Jianwei Jiao

doi:10.1016/j.cell.2026.04.040

Decoding the spatiotemporal development of human meninges

Cell. 2026 May 29:S0092-8674(26)00507-6. doi: 10.1016/j.cell.2026.04.040. Online ahead of print.

Authors

Yanxin Li¹, Zhongqiu Li², Yong She³, Ziqing He⁴, Changliang Wang⁴, Yuehong Zhang⁵, Rong Li⁶, Lei Jin⁷, Fen Ji⁸, Peng Du⁹, Ji Dong¹⁰, Jianwei Jiao¹¹

Affiliations

¹ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Cell Biology, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
² State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; School of Convergence medicine, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Zhengzhou University, Zhengzhou 400015, China. Electronic address: lizhongqiu@ioz.ac.cn.
³ Guangzhou National Laboratory, Guangzhou 510005, China; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
⁴ Guangzhou National Laboratory, Guangzhou 510005, China.
⁵ Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, China.
⁶ Department of Obstetrics and Gynecology, Ministry of Education, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
⁷ Institute of Reproductive and Child Health, Peking University, National Health Commission Key Laboratory, Peking University, Beijing 100191, China.
⁸ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
⁹ MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, China.
¹⁰ Guangzhou National Laboratory, Guangzhou 510005, China. Electronic address: dong_ji@gzlab.ac.cn.
¹¹ State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China. Electronic address: jwjiao@ioz.ac.cn.

PMID: 42214341
DOI: 10.1016/j.cell.2026.04.040

Abstract

The human meninges are essential regulators of central nervous system (CNS) development and homeostasis. However, a comprehensive spatiotemporal characterization of the cellular and molecular dynamics during human meninges development is currently lacking. Using single-cell spatiotemporal transcriptomics across 6-23 gestational weeks (GWs), we identify asynchronous meningeal layer development, with the pia mater forming earliest. We define layer-specific fibroblast states from the three meningeal layers, including the expression of barrier-related genes, neurotransmitter transporter-related and synapse-related genes, and lipid metabolism-related genes. We further characterize spatiotemporal heterogeneity in meningeal immune cells, identifying a meningeal-specific macrophage population. The pia mater recruits and spatially organizes immune cells, particularly macrophages in the leptomeninges via CXCL12-CXCR4 signaling. Moreover, Trem2⁺ macrophages, in turn, regulate the development of Cajal-Retzius (CR) cells in the cerebral cortex. These findings establish a spatiotemporal framework for human meningeal development, uncover neuro-immune interactions that shape cortical development, and identify potential therapeutic targets.

Keywords: MERFISH; human meningeal development; meningeal angiogenesis; meningeal fibroblasts; meningeal macrophages; neuro-immune interaction; pial fibroblasts; scRNA-seq; scStereo-seq; spatial transcriptomics.