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Biology subjects

Maderna, C.

Publications and source records attributed to Maderna, C..

2 recordsLinked to original sources

SP2G: an imaging and analysis pipeline revealing the inter and intra-patient migratory diversity of glioblastoma

Glioblastomas are heterogeneous, primary brain tumors hiding several sub-populations. Patient-derived xenografts are considered gold-standards to study glioblastoma invasion. However, they present many disadvantages, including time consumption, complex standardization, high cost. To counteract these issues and rapidly identify the most invasive sub-populations, we developed an in vivo mimicry platform named SP2G (SPheroid SPreading on Grids). Live imaging of tumor-derived spheroids spreading on gridded micro patterns mimicking the brain vasculature recapitulated 3D motility features observed in brain or 3D matrices. Using patient-derived samples coupled with a semi-automated macro suite, SP2G easily characterized and sorted differences in cell migration and motility modes. Moreover, SP2G exposed the hidden intra-patient heterogeneity in cell motility that correlated molecularly to specific integrins. Thus, SP2G constitute a versatile and potentially pan-cancer workflow to identify the diverse invasive tumor sub-populations in patient-derived specimens. SP2G includes an integrative tool, available as open-source Fiji macro suite, for therapeutic evaluations at single patient level. TeaserCracking the inter and intra-patient diversity in Glioblastoma migration profiles

biophysics↗

Dual role of brain endothelial Gpr126 in blood-brain barrier development and ischemic stroke

The blood-brain barrier (BBB) acquires unique properties for regulation of the neuronal function during development. The genesis of the BBB coupled with angiogenesis is orchestrated by the Wnt/{beta}-catenin signaling pathway. Aside from the importance of Wnt/{beta}-catenin signaling, the molecular mechanisms that regulate these processes are poorly understood. Here, we identify the brain endothelial adhesion G-protein-coupled receptor Gpr126 as a novel target gene of Wnt/{beta}-catenin signaling that is required for postnatal BBB development, and its expression is detrimental for ischemic stroke in adults. We show that Gpr126 expression is high in mouse brain endothelium during BBB formation, but decreases in the adult. Inactivation of Gpr126 in postnatal endothelial cells results in vessel enlargement and impairs acquisition of the BBB characteristics, such as increased neurovascular permeability, and reduced basement membrane protein deposition and pericyte coverage. Mechanistically, Gpr126 is required during developmental angiogenesis to promote endothelial cell migration, acting via an interaction between Lrp1 and 3{beta}1-integrin, which couples vessel morphogenesis to BBB formation. Interestingly, in adult mice with an established BBB, the lack of Gpr126 expression in acute ischemic stroke is protective and coupled with reduced microglia activation, which contributes to an improved neurological outcome. These data identify Gpr126 as a promising therapeutic target to treat ischemic stroke.

cell biology↗