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Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain.
Chen, Jiapei; Crouch, Elizabeth E; Zawadzki, Miriam E; Jacobs, Kyle A; Mayo, Lakyn N; Choi, Jennifer Ja-Yoon; Lin, Pin-Yeh; Shaikh, Saba; Tsui, Jessica; Gonzalez-Granero, Susana; Waller, Shamari; Kelekar, Avani; Kang, Gugene; Valenzuela, Edward J; Birrueta, Janeth Ochoa; Diafos, Loukas N; Wedderburn-Pugh, Kaylee; Di Marco, Barbara; Xia, Wenlong; Han, Claudia Z; Coufal, Nicole G; Glass, Christopher K; Fancy, Stephen P J; Alfonso, Julieta; Kriegstein, Arnold R; Oldham, Michael C; Garcia-Verdugo, Jose Manuel; Kutys, Matthew L; Lehtinen, Maria K; Combes, Alexis J; Huang, Eric J.
Afiliação
  • Chen J; Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Crouch EE; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
  • Zawadzki ME; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
  • Jacobs KA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Mayo LN; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Choi JJ; Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • Lin PY; Harvard/MIT MD-PhD Program, Harvard Medical School, Boston, MA, USA.
  • Shaikh S; Graduate Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA, USA.
  • Tsui J; Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.
  • Gonzalez-Granero S; Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.
  • Waller S; UCSF-UC Berkeley Joint Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA.
  • Kelekar A; Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Kang G; Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Valenzuela EJ; UCSF CoLab, University of California San Francisco, San Francisco, CA, USA.
  • Birrueta JO; UCSF CoLab, University of California San Francisco, San Francisco, CA, USA.
  • Diafos LN; Laboratory of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia and CIBERNED-ISCIII, Valencia, Spain.
  • Wedderburn-Pugh K; Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Di Marco B; Department of Pathology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Xia W; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Han CZ; Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, CA, USA.
  • Coufal NG; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Glass CK; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Fancy SPJ; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Alfonso J; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Kriegstein AR; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
  • Oldham MC; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
  • Garcia-Verdugo JM; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
  • Kutys ML; Medical Scientist Training Program, University of California San Francisco, San Francisco, CA, USA.
  • Lehtinen MK; Department of Clinical Neurobiology, University Hospital Heidelberg and German Cancer Research Center, Heidelberg, Germany.
  • Combes AJ; Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Huang EJ; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Nat Neurosci ; 2024 Sep 30.
Article em En | MEDLINE | ID: mdl-39349662
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Nat Neurosci Assunto da revista: NEUROLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos