Identification of secondary microglial formation centers in the human fetal brain.
Overview
- Department of Anatomy and Histology & Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Department of Neurology, Minhang Hospital, Fudan University, Shanghai, China
- Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China
- Department of Pathology, Shanghai Key Laboratory of Maternal-Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
Abstract
Microglia migrate from the yolk sac and populate the developing brain. How microglia expand rapidly to meet the microglial demand in fast-expanding human fetal brains remains uncharted. Using thick sections in 5−22–gestational week (gw) brains and super-resolution scanning, we identified a large proliferative microglial aggregate (2.129 mm2) near the lateral ganglionic eminence (>12.5 gw), expanding in Down’s syndrome (DS) (4.767 mm2) and Edwards syndrome (ES) (3.437 mm2) fetal brains. Ki67+ microglia within the aggregates accounted for 26.65% (DS: 38.9%; ES: 46.3%) compared with 6.32% (DS: 6.01%; ES: 5.2%) in scattered microglia. This aggregate region contained a distinct microglial population characterized by the absence of phagocytic structures and complex processes, high CSF-1R expression, abundant IL-34+ cells, and some SPP1+ bipolar microglia. We termed this structure the secondary microglial formation center (SMFC). Chimeric microglia–human cortical organoids recapitulated the SMFC in an IL-34– and CSF-1R–dependent manner, indicating that the human SMFC may compensate for the microglial shortage during the fastest expansion period.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- bioproject:PRJNA1152524, at NCBI BioProject; found in “Data availability”
Data availability
All relevant data are included in the paper and are available upon reasonable request. The bulk RNA-seq and proteomic datasets generated and/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 2, 28 September 2026
- Publisher: n/a → Rockefeller University Press
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 7 MeSH terms, 2 funders, 51 references.
Cite
This paper
Song, C., Chen, X., Ji, R., Liu, Y., Han, Y., Ye, F., Zhang, L., Li, L., Gao, L., He, Q., Ma, L., & Saiyin, H. (2026). Identification of secondary microglial formation centers in the human fetal brain. The Journal of experimental medicine, 223(6), e20251801. https://
BibTeX
@article{song2026identif
author = {Song, Chenyun and Chen, Xinyu and Ji, Rong and Liu, Yang and Han, Yawen and Ye, Fangzhou and Zhang, Ling and Li, Li and Gao, Lu and He, Qizhi and Ma, Lixiang and Saiyin, Hexige},
title = {{Identification of secondary microglial formation centers in the human fetal brain}},
journal = {The Journal of experimental medicine},
year = {2026},
month = may,
volume = {223},
number = {6},
pages = {e20251801},
publisher = {Rockefeller University Press},
issn = {0022-1007},
doi = {10.1084/
url = {https://
pmid = {42149661},
pmcid = {PMC13182777}
}
RIS
TY - JOUR
AU - Song, Chenyun
AU - Chen, Xinyu
AU - Ji, Rong
AU - Liu, Yang
AU - Han, Yawen
AU - Ye, Fangzhou
AU - Zhang, Ling
AU - Li, Li
AU - Gao, Lu
AU - He, Qizhi
AU - Ma, Lixiang
AU - Saiyin, Hexige
TI - Identification of secondary microglial formation centers in the human fetal brain
T2 - The Journal of experimental medicine
J2 - J Exp Med
PY - 2026
DA - 2026/
VL - 223
IS - 6
SP - e20251801
SN - 0022-1007
PB - Rockefeller University Press
DO - 10.1084/
UR - https://
LA - en
ER -
CSL-JSON
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