Hematopoietic Stem and Progenitor Cells Use Podosomes to Transcellularly Home to the Bone Marrow
Hematopoietic Stem and Progenitor Cells Use Podosomes to Transcellularly Home to the Bone Marrow
ABSTRACT Bone marrow (BM) endothelium plays an important role in homing of hematopoietic stem and progenitor cells (HSPCs) upon transplantation, but surprisingly little is known on how endothelial cells regulate local permeability and HSPC transmigration. We show that temporal loss of VE-cadherin function promotes vascular permeability in BM, even upon low dose irradiation and strongly enhanced homing of transplanted HSPCs to BM of irradiated mice. Intriguingly, stabilizing junctional VE-cadherin in vivo reduced BM permeability, but did not prevent HSPC migration into the BM, suggesting that HSPCs enter the bone marrow by transcellularly crossing the endothelium. Indeed, HSPCs induce podosomes to cross human BM endothelial monolayers in a transcellular manner. By contrast, HSPC rather use the paracellular route when VE-cadherin function is inhibited. Taken together, VE-cadherin is crucial for BM vascular homeostasis and HSPC homing, and may therefore serve as a potential therapeutic target to improve HSPC homing strategies.
Rademakers Timo、Goedhart Marieke、Butz Stefan、Huveneers Stephan、van Buul Jaap D.、Schnoor Michael、Samus Maryna、Hoogenboezem Mark、Nolte Martijn A.、Voermans Carlijn、Garc¨aa Ponce Alexander、Vestweber Dietmar、van Rijssel Jos
Dept. Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterDept. Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterMax Planck Institute for Molecular BiomedicineDept. of Medical Biochemistry, Academic Medical CenterDept. Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterDepartment for Molecular Biomedicine, Center of Research and Advanced Studies (CINVESTAV-IPN)Max Planck Institute for Molecular BiomedicineDept. Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterDept. Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterDept. Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical CenterDepartment for Molecular Biomedicine, Center of Research and Advanced Studies (CINVESTAV-IPN)Max Planck Institute for Molecular BiomedicineDept. Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center
基础医学细胞生物学生理学
HomingVE-cadherinBone marrowstem and progenitor cellPermeabilityTransmigration
Rademakers Timo,Goedhart Marieke,Butz Stefan,Huveneers Stephan,van Buul Jaap D.,Schnoor Michael,Samus Maryna,Hoogenboezem Mark,Nolte Martijn A.,Voermans Carlijn,Garc¨aa Ponce Alexander,Vestweber Dietmar,van Rijssel Jos.Hematopoietic Stem and Progenitor Cells Use Podosomes to Transcellularly Home to the Bone Marrow[EB/OL].(2025-03-28)[2025-08-21].https://www.biorxiv.org/content/10.1101/269704.点此复制
评论