Cellular and molecular mechanisms of blood-brain barrier formation and maintenance

• Applicant: Professor Dr. Ralf H. Adams
• Subject Area: Developmental Neurobiology ; Developmental Biology ; Cell Biology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391580220

• Final Report Year: 2022

Final Report Abstract

The brain vasculature prevents the entry of potentially harmful substances and immune cells from the circulation and thereby protects the functionality of neuronal networks. This blood-brain barrier, which involves tight interactions between endothelial cells, pericytes and astrocytes, is critical for the healthy organism and, accordingly, its breakdown is a hallmark of human diseases such as stroke, neurodegeneration and multiple sclerosis. Our project has generated new insight into the molecular properties of brain pericytes and their regulation by Yap1 and Taz, which are transcriptional coregulators acting in the Hippo signaling pathway. We also performed single cell RNA sequencing after demyelination, which results in the strong enrichment of non-neuronal cell populations from brain. This revealed changes in the murine cerebral cortex during development, adulthood, ageing and neuroinflammation. We also identified a subset of post-capillary venules, which are characterized by expression of cell adhesion molecules, preferential leukocyte transmigration, association with perivascular macrophage populations, and endothelial activation initiating immune responses in the central nervous system.

Publications

• Genetic Lineage Tracing of Nonmyocyte Population by Dual Recombinases. Circulation. 2018 Aug 21;138(8):793-805
  Li Y, He L, Huang X, Bhaloo SI, Zhao H, Zhang S, Pu W, Tian X, Li Y, Liu Q, Yu W, Zhang L, Liu X, Liu K, Tang J, Zhang H, Cai D, Adams RH, Xu Q, Lui KO, Zhou B
  
• Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury. Cell Stem Cell. 2019 Dec 5;25(6):768-783.e6
  Chen Q, Liu Y, Jeong HW, Stehling M, Dinh VV, Zhou B, Adams RH
  
• A molecular map of murine lymph node blood vascular endothelium at single cell resolution. Nat Commun. 2020 Jul 30;11(1):3798
  Brulois K, Rajaraman A, Szade A, Nordling S, Bogoslowski A, Dermadi D, Rahman M, Kiefel H, O'Hara E, Koning JJ, Kawashima H, Zhou B, Vestweber D, Red-Horse K, Mebius RE, Adams RH, Kubes P, Pan J, Butcher EC
  
• Donor cell memory confers a metastable state of directly converted cells. Cell Stem Cell. 2021 Jul 1;28(7):1291-1306.e10
  Kim KP, Li C, Bunina D, Jeong HW, Ghelman J, Yoon J, Shin B, Park H, Han DW, Zaugg JB, Kim J, Kuhlmann T, Adams RH, Noh KM, Goldman SA, Schöler HR
  
• Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells. Cardiovasc Res. 2021 Jan 1;117(1):256-270
  Kocijan T, Rehman M, Colliva A, Groppa E, Leban M, Vodret S, Volf N, Zucca G, Cappelletto A, Piperno GM, Zentilin L, Giacca M, Benvenuti F, Zhou B, Adams RH, Zacchigna S