TY  - JOUR
AU  - Chen, Jiapei
AU  - Crouch, Elizabeth E
AU  - Zawadzki, Miriam E
AU  - Jacobs, Kyle A
AU  - Mayo, Lakyn N
AU  - Choi, Jennifer Ja-Yoon
AU  - Lin, Pin-Yeh
AU  - Shaikh, Saba
AU  - Tsui, Jessica
AU  - Gonzalez-Granero, Susana
AU  - Waller, Shamari
AU  - Kelekar, Avani
AU  - Kang, Gugene
AU  - Valenzuela, Edward J
AU  - Birrueta, Janeth Ochoa
AU  - Diafos, Loukas N
AU  - Wedderburn-Pugh, Kaylee
AU  - Di Marco, Barbara
AU  - Xia, Wenlong
AU  - Han, Claudia Z
AU  - Coufal, Nicole G
AU  - Glass, Christopher K
AU  - Fancy, Stephen P J
AU  - Alfonso, Julieta
AU  - Kriegstein, Arnold R
AU  - Oldham, Michael C
AU  - Garcia-Verdugo, Jose Manuel
AU  - Kutys, Matthew L
AU  - Lehtinen, Maria K
AU  - Combes, Alexis J
AU  - Huang, Eric J
TI  - Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain.
JO  - Nature neuroscience
VL  - 27
IS  - 11
SN  - 1097-6256
CY  - New York, NY
PB  - Nature America
M1  - DKFZ-2024-01961
SP  - 2115-2129
PY  - 2024
N1  - 2024 Nov;27(11):2115-2129
AB  - Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45+ cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45+ cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain's innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants.
LB  - PUB:(DE-HGF)16
C6  - pmid:39349662
DO  - DOI:10.1038/s41593-024-01769-2
UR  - https://inrepo02.dkfz.de/record/293803
ER  -