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Despite their critical functions, our understanding of leptomeningeal development and maturation during human embryogenesis remains limited. This study seeks to bridge this gap.<\/jats:p>\n               <jats:p>We conducted single-nucleus RNA sequencing on leptomeningeal tissues from eight human embryos, capturing developmental stages from early fetal to late mid-fetal phases. Our bioinformatic analyses encompassed cell type classification, identification of layer-specific markers, mapping of the arachnoid barrier maturation trajectory, and joint analyses with mouse and aged human leptomeningeal single-cell RNA sequencing (scRNA-seq) datasets datasets. Key bioinformatic findings were validated through immunostaining in selected samples.<\/jats:p>\n               <jats:p>Our study revealed a complex cellular heterogeneity within the developing leptomeninges, identifying distinct subpopulations of fibroblasts, immune cells and vascular cells. We mapped the transcriptomic dynamics of fibroblast cell types throughout fetal brain development, highlighting a clear maturation process from early fetal to late mid-fetal stages. Comparative analysis with mouse data allowed us to distinguish human-specific layer markers while confirming several conserved markers shared between humans and mice. Joint analysis with aged human datasets identified two unique arachnoid clusters specific to ageing leptomeninges. Moreover, we traced the developmental trajectory of the arachnoid barrier, detailing the transcriptomic shifts associated with its gradual formation. Notably, immune cells in early fetal stages were predominantly M2-type macrophages, underscoring a distinctive immune environment. Finally, we explored the molecular interactions between fibroblasts and other cell types, highlighting their coordinated roles in orchestrating leptomeningeal development.<\/jats:p>\n               <jats:p>Together, our findings provide a comprehensive overview of the cellular and molecular landscape of the developing human leptomeninges.<\/jats:p>","DOI":"10.1093\/brain\/awae397","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T22:54:42Z","timestamp":1733871282000},"page":"2218-2232","source":"Crossref","is-referenced-by-count":13,"title":["Deciphering the temporal transcriptional landscape of human fetal leptomeninges"],"prefix":"10.1093","volume":"148","author":[{"given":"Licheng","family":"Sun","sequence":"first","affiliation":[{"name":"Department of General Surgery, Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University , Shanghai 200090 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University , Shanghai 200090 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuantao","family":"Fang","sequence":"additional","affiliation":[{"name":"Shanghai Tenth People\u2019s Hospital, Institute for Infectious Diseases and Vaccine Development, Tongji University School of Medicine , Shanghai 200072 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Family Planning, Changning Maternity and Infant Health Hospital , Shanghai 200050 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Shanghai , Shanghai 200333 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Institute of Pediatrics, Children\u2019s Hospital of Fudan University and Huashan Hospital of Fudan University, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Instituto de Agroecolox\u00eda e Alimentaci\u00f3n (IAA) \u2013 CITEXVI , 36310 Vigo ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Institute of Pediatrics, Children\u2019s Hospital of Fudan University and Huashan Hospital of Fudan University, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Yale School of Medicine , New Haven, CT 06510 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Center for Clinical Research and Translational Medicine, Yangpu Hospital, 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