Biology subjects

Taib, S.

Publications and source records attributed to Taib, S..

3 recordsLinked to original sources

bioRxiv2024

Vascular dysfunction is at the onset of oxaliplatin-induced peripheral neuropathy symptoms in mice

Oxaliplatin-induced peripheral neuropathy (OIPN) is an adverse side effect of this chemotherapy used for gastrointestinal cancers. The continuous pain experienced by OIPN patients often result in the reduction or discontinuation of chemotherapy, thereby affecting patient survival. Several pathogenic mechanisms involving sensory neurons were shown to participate in the occurrence of OIPN symptoms. However, the dysfunction of the blood-nerve barrier as a source of nerve alteration had not been thoroughly explored. To characterise the vascular contribution to OIPN symptoms, we undertook two comparative transcriptomic analyses from mouse purified brain and sciatic nerve blood vessels (BVs), and nerve BVs after oxaliplatin or control administration. These analyses reveal distinct molecular landscapes between brain and nerve BVs and the upregulation of transcripts involved in vascular contraction after oxaliplatin treatment. Anatomical examination of the nerve yet shows the preservation of BV architecture in acute OIPN mouse model, although treated mice exhibit both neuropathic symptoms and enhanced vasoconstriction reflected by hypoxia. Moreover, vasodilators significantly reduce oxaliplatin-induced neuropathic symptoms and endoneurial hypoxia, establishing the key involvement of nerve blood flow in OIPN.

neuroscience↗

bioRxiv2023

Uncovering the transcriptomic heterogeneity of pancreatic endothelial cells using integrative and comparative single cell gene expression analysis

The pancreatic islet vasculature displays tissue-specific physiological and functional adaptations that support rapid glucose sensing and insulin response by {beta}-cells. To uncover the transcriptomic basis of this specialization, we performed a meta-analysis of multi-organ single cell RNA sequencing atlases employing a unique strategy to avoid transcriptomic contamination. We identified biologically relevant genes involved in sphingosine-1-phosphate-mediated insulin-secretion (PLPP1, RDX, CDC42EP1), islet basement membrane formation (SPARC, COL15A1), endothelial cell (EC) permeability (PLVAP, EHD4), membrane transporters (CD320, SLCO2A1) and developmental transcription factors (NKX2-3, AHR). These were validated in silico in independent datasets. We further established the first integrated transcriptomic atlas of human pancreatic ECs and described two unique capillary subpopulations: exocrine and endocrine pancreas ECs. We validated the spatial localization of key markers using RNAscope and immunofluorescence staining on mouse pancreatic tissue cross-sections. Our findings provide novel insights into pancreatic EC heterogeneity and islet EC function with potential implications in therapeutic strategies.

cell biology↗

bioRxiv2021

Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC); this rare type of leukodystrophy is characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes (PvAPs, which along with blood vessels form the gliovascular unit (GVU)). We analyzed the GVU in the Mlc1 knock-out mouse model of MLC. The absence of MLC1 led to an accumulation of fluid in the brain but did not modify the endothelial organization or the integrity of the blood-brain barrier. From P10 onward, the postnatal acquisition of vascular smooth muscle cell contractility was altered, resulting in a marked reduction in arterial perfusion and neurovascular coupling. These anomalies were correlated with alterations in astrocyte morphology, astrocyte polarity and the structural organization of the PvAPs perivascular coverage, and poor intraparenchymal circulation of the cerebrospinal fluid (CSF). Hence, MLC1 is required for the postnatal development and organization of PvAPs and controls vessel contractility and intraparenchymal interstitial fluid clearance. Our data suggest that (i) MLC is a developmental disorder of the GVU, and (ii) PvAP and VSMC maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.

neuroscience↗